Nanotech – the science of building and manipulating structures at the molecular level – promises fresh perspectives on and unexpected solutions to a wide range of existing problems in semiconductors, optics, sensing, and biotechnology. Many of this year’s TR100 honorees, determined to make new breakthroughs, are turning to nanotechnology to gain an unprecedented level of precision, control, and flexibility in creating new materials and devices. The nanomaterials invented by this elite group promise everything from faster and smaller electronics to more effective and targeted therapies. “When you get to the nano length scales, you can get unique properties,” says Yi Cui of the University of California, Berkeley. The TR100’s Nanotech+ category includes a broad range of innovations and research in materials science and energy. But it is on the scale of the ultrasmall that many of this year’s TR100 are making their biggest contributions.

Much of the action is in biomedicine. That’s because nanomaterials are just the right size to interact with important biological actors, such as proteins, DNA molecules, and viruses. Applying nanotech to biomedical problems “is a natural fit,” says Darrell Irvine, a biomedical-engineering professor at MIT.

Irvine is helping to build better vaccines against diseases such as malaria and cancer by designing nanoparticles of a synthetic polymer. The nanoparticles, which carry specific stimulating molecules and antigens, are taken up by immune cells, triggering an immune response. Because of their tiny size, the nanoparticles can deliver the molecules with a high level of precision to specific receptors inside cells. That means better control of the strength and type of the resulting immune response, which should make for more effective vaccines. Irvine has recently begun working with medical researchers at Harvard University to investigate materials that could be used to deliver an HIV vaccine.

Albena Ivanisevic, a chemistry professor at Purdue University, is employing a technique called dip-pen nanolithography to help solve a central problem for tissue engineers hoping to repair damaged body parts: controlling the precise growth of cells at specific locations. Ivanisevic coats microscopic tips with cell-nourishing peptide molecules; the tips then deposit the peptides onto a surface. The ability to arrange those peptide molecules with nanoscale precision gives Ivanisevic greater control over how and where cells will grow on the surface – ultimately forming new tissue for the body.

Nanotech also opens up new possibilities for those working to more effectively exploit or manipulate light. As anyone who has ever had to change a light bulb might suspect, conventional incandescent lighting is based on a 150-year-old technology, and researchers are eagerly looking for new ways to extend the lifetimes and boost the efficiencies of light-emitting materials. One of the favorite toys of researchers in the field is quantum dots – nanoparticles of semiconductor material that give off different colors of light depending on their size. And Vladimir Bulovic, a professor of electrical engineering at MIT, is using these hardy, brightly colored nano dots to reinvent the light bulb. From quantum dots, Bulovic has built novel light-emitting diodes that can be incorporated into flexible materials like plastic and should last much longer than typical light bulbs. While others, including Bulovic himself, have already developed organic light-emitting diodes, Bulovic says quantum dots can extend their effective lifetime, making them more widely usable. He’s hoping to produce a highly efficient and long-lasting light-emitting flexible material in the next one to two years.

Marcel Bruchez, lead product development scientist at Quantum Dot of Hayward, CA, is also enlisting the glowing nanoparticles, but for biological imaging and the development of diagnostics. Quantum dots emit light for much longer than the conventional dyes used to track activity inside living cells, and their varied colors mean that researchers can simultaneously image multiple events and gain greater insight into the inner workings of cells. For Bruchez, the benefit of working with nanomaterials is that they open up whole new ways of thinking about problems. “It gives you greater flexibility in manipulating the materials and in putting them where you want them to go,” says Bruchez.

Electronics researchers pursuing ever smaller and faster circuits are also making strides with the help of nanotech. “The silicon industry is already in the nano regime,” points out Kinneret Keren, a researcher at Stanford University. “Now they’re trying more for the molecular regime.” That means using molecules such as carbon nanotubes to build next-generation electrical circuits. While other researchers have already made transistors out of individual semiconducting nanotubes, Keren decided to address the process of assembling such transistors. Her trick was to attach complementary pieces of DNA to a nanotube and to a silicon wafer; because the two pieces of DNA naturally bound to each other, they did the work of bringing the nanotube and the wafer together so as to produce a transistor. While Keren’s process remains a laboratory feat, it could eventually offer a new method of efficiently manufacturing tiny circuits in which each transistor is a single molecule.

While researchers like Keren recruit biomolecules to help fabricate electronics, Mayank Bulsara is sticking with traditional silicon – but manipulating it in new ways. Bulsara, cofounder and chief technology officer of AmberWave Systems of Salem, NH, is developing a new form of silicon that promises to make computer chips 20 percent faster while lowering power consumption by 30 to 40 percent. The key is to stretch a silicon crystal by pulling its atoms apart just a few thousandths of a nanometer – “like a rubber band,” says Bulsara. This stretching alters the properties of the material so that the electrons racing through it are less likely to collide with silicon atoms, scatter, and slow down. Bulsara hopes to have chips containing the stretched silicon on the market in major quantities by the end of next year.

This year’s TR100 are just beginning to demonstrate the results of nanotech’s forays into exciting new territories, but taking their work out into the real world poses its own problems. “The greatest challenge is coming up with ways of producing nanomaterials over large enough areas,” says Bulovic. But when that challenge is finally met, don’t be surprised if the rising stars you’ll read about in the next few pages were among those who helped point the way.

Nanotech Profiles

Marcel Bruchez
Age: 31 | Cofounder and principal staff scientist | Quantum Dot
Six years ago, Marcel Bruchez, then a graduate student at the University of California, Berkeley, showed that quantum dots – glowing particles just nanometers wide – could be used to tag proteins inside cells. Within months, Bruchez had cofounded Quantum Dot to market the new imaging tool to biologists and drug developers seeking a more detailed picture of molecular events. It is “one of the first commercial applications of nanotechnology,” says Bruchez.

Yi Cui
Age: 28 | Research fellow | University of California, Berkeley
While some nanotech researchers create the basic building blocks of new materials, others, like Yi Cui, play equally important roles in piecing those blocks together and taking the next steps toward practical applications. Cui’s ability to finely control the assembly of nano building blocks has led to new devices that may end up in cancer-screening chips, quantum computers, and solar cells.

As a chemistry PhD student at Harvard University, Cui did pioneering work on nanowires, using a combination of lasers and chemical vapors to cajole silicon to form tiny wires that not only conducted electrons but could also switch a current off and on like a transistor. Cui even fabricated nanowires whose switching depended on the presence of specific proteins, so they could serve as ultrasensitive biosensors in tests for early signs of prostate cancer.

At Berkeley, Cui has continued to master the art of building functional devices on the nanoscale. Most recently, he has found ways to precisely link together new types of nano building blocks called nanotetrapods – dots of material a few nanometers wide, each with four nanorods that radiate out in different directions. While other researchers have previously made nanotetrapods, Cui can link many of them together to create a web of circuitry and finely control their electrical properties. “We can get the nanotetrapods to self-assemble into whatever pattern we need,” including arrays of transistors, says Cui. Because of their small size, these circuits could in theory be several times faster than the circuits in today’s computer chips.

By arranging nanotetrapods into branching networks, Cui has transformed them from a raw ingredient into something that might be built into real devices, such as solar cells. And because the nanotetrapods are small enough to register the presence of individual electrons, they could even take advantage of the weird quantum properties of subatomic particles, forming the basis for new types of computers that will operate thousands of times faster than today’s fastest machines. While that application is many years away, Cui has already demonstrated the possibility of building new structures using the basic ingredients of nanotech.

Leroy Ohlsen
Age: 30 | Founder and chief technology officer | Neah Power Systems
Fuel cells that run on methanol can power cell phones and laptops, but they’re expensive and not very powerful. Leroy Ohlsen, founder of Neah Power Systems of Bothell, WA, replaced the cells’ plastic membranes, which strip electrons out of the methanol to produce electricity, with porous silicon. Not only does the silicon “give us more power,” says Ohlsen, but it could also cut manufacturing costs. Expect the company’s first fuel cells in 2006.

Molly Stevens
Age: 30 | Lecturer | Imperial College London
Materials scientist Molly Stevens believes that when it comes to sensing changes in the environment, nothing beats biological systems. That’s why she’s turning to biological molecules to create “smart” nanomaterials that could lead to new, implantable sensing and drug delivery devices.

Such devices would quickly detect physiological changes in the body, such as a rise in cholesterol, and respond by releasing the appropriate dose of a stored drug. That’s the vision, at least. But realizing it will require new kinds of materials that behave differently under different chemical conditions.

Stevens has recently shown that she can control the behavior of gold nanoparticles by changing the pH of the solution in which they are suspended. She attached the particles to specially designed peptide molecules that, under the right pH conditions, interact with each other to pull the particles together into an organized structure. A change in pH alters the shape of the peptides so that they repel each other, and the particles disperse. “We’re taking the best of nature’s creativity and using it for ourselves,” says Stevens.

The experiment shows that it’s possible to create materials that automatically reshape themselves in response to chemical changes in the body. Such a material could yield implantable drug delivery devices that act as their own biological sensors.

Stevens is tapping into the versatility of peptides for the next stage of her work. She’s now engineering the peptides so that they change shape in subtler and more varied ways. A drug delivery device made using such peptides would be more sensitive to physiological changes and could offer more control over a multitude of different drug dosages. If her new project succeeds, Stevens will have played an instrumental role in making not only nanomaterials but drug delivery far smarter.

Vladimir Bulovic
Age: 34
Associate professor, MIT
Uses organic and nanostructured semiconductors in devices such as light-emitting diodes, lasers, photodetectors, and chemical sensors. Startup companies have licensed many of his 30 U.S. patents.

Mayank Bulsara
Age: 32
Cofounder and chief technology officer, AmberWave Systems
Cofounded Salem, NH-based AmberWave to develop strained silicon, an advanced form of silicon that makes computer chips run faster and consume less power.

Dustin Carr
Age: 34
Principal member of technical staff, Sandia National Laboratories
Creates nanoscale silicon devices that can detect subatomic-scale movements. The nanodetectors could be used, for instance, in ultraprecise accelerometers for airplane navigation.

Martin Culpepper
Age: 32
Assistant professor, MIT
Builds the machines needed to make high-quality, low-cost nanofabrication a reality. His nanomanipulators are more flexible and offer higher performance than existing versions – at one-twentieth the cost.

LÆtitia Delmau
Age: 33
Research staff member, Oak Ridge National Laboratory
Helped solve fundamental problems in nuclear-waste treatment that led to an economical process for cleaning up more than 100,000 cubic meters of radioactive waste at the Savannah River Site in South Carolina, which manages the U.S. nuclear stockpile.

Martha Gardner
Age: 33
Statistician, General Electric
Created statistical models and design software to make materials development more efficient. Using her methods, engineers have cut product development time by 90 percent.

Verena Graf
Age: 32
Engineer, DaimlerChrysler
Develops fuel cells that are practical for powering cars: they’re robust, start up quickly, and have excellent power density, regardless of the weather.

Yu Han
Age: 27
Postdoctoral fellow, Institute of Bioengineering and Nanotechnology (Singapore)
Synthesized nanoscale particles with tiny, precisely defined pores. His materials can be used for the controlled delivery of drugs or for gene therapy.

Stefan Hecht
Age: 30
Assistant professor, Freie Universität Berlin
Devised a new class of polymer nanotubes and other molecular building blocks. These novel materials have potential applications in the fabrication of nanosized electronic devices.

Darrell Irvine
Age: 31
Assistant professor, MIT
Crafts nanoparticles that would release chemicals inside the body to “program” immune cells to combat viral infections like HIV, to tolerate transplants, or even to destroy malignant tumors.

Rustem Ismagilov
Age: 31
Assistant professor, University of Chicago
Develops microfluidics technologies that use tiny droplets to characterize the function and structure of proteins and to model complex biochemical processes. The microfluidic models should yield insights pertinent to drug discovery and medical-device design.

Albena Ivanisevic
Age: 29
Assistant professor, Purdue University
Uses microscopic tips to deposit precise patterns of peptides directly onto tissues in the body. Her technique, which she’s testing in pigs’ eyes, could help treat or even cure blindness.

Ravi Kane
Age: 32
Assistant professor, Rensselaer Polytechnic Institute
Created a highly potent anthrax treatment in which each drug molecule blocks multiple toxin molecules rather than just one. He’s extending the concept to anti-HIV therapies.

Kinneret Keren
Age: 32
Postdoctoral fellow, Stanford University Medical School
Exploits biology-based self-assembly to build molecular electronics. She created a self-assembled molecular-electronic device – a carbon nanotube transistor – using a DNA template.

Jamie Link
Age: 26
Doctoral student, University of California, San Diego
Etched optical bar codes into micrometer-size pieces of silicon. She hopes to use the technology to detect pollutants in water or cancerous cells within the body.

Yueh-Lin (Lynn) Loo
Age: 30
Assistant professor, University of Texas at Austin
Invented nano transfer printing, an environmentally benign technique for patterning nanoscale features on organic electronics and plastic circuits. This nano patterning scheme could be used to make large-area flexible displays and cheap solar cells, and it could enable new medical therapies and diagnostics.

Tyler McQuade
Age: 33
Assistant professor, Cornell University
Creates catalysts to reduce the number of steps needed to synthesize drugs, diminishing environmentally hazardous by-products. He hopes one system will take the manufac-ture of Prozac, a top-selling anti-depressant drug, from four steps to just one.

Teri Odom
Age: 30
Assistant professor,
Northwestern University
Patterned silicon to create minuscule “beakers” that hold only zeptoliters (the silicon nanowells are only 50 nanometers across), ideal for growing individual nanoparticles of specific and uniform size. Such ultraprecision enables the tailoring of particles to specialized uses – as, for instance, ultrasensitive chemical sensors.

Erik Scher
Age: 28
Research and development scientist, Nanosys
Works on inorganic semiconductor nanomaterials that are helping Palo Alto, CA-based Nanosys develop cheap, flexible solar cells. Nanosys’s partner, Matsushita, plans to incorporate the nano solar cells into building materials.

Michael Strano
Age: 28
Assistant professor, University of Illinois, Urbana-Champaign
Arrived at a new understanding of carbon nanotube surface chemistry that allows carbon nanotubes to be sorted according to their semiconducting, metallic, or insulating properties. This breaks the major roadblock that has prevented nanotubes’ use in devices.

William Taylor
Age: 32
Director of engineering, ArvinMeritor
Spearheads efforts to commercialize the “plasmatron,” a pollution control device that converts diesel fuel to hydrogen, cutting nitrogen oxide emissions by up to 90 percent.

Tsuyoshi Yamamoto
Age: 31
Researcher, NEC
Demonstrated the first-ever two-qubit logic gate in a solid-state device, an advance crucial to building an ultrafast quantum computer.

Shu Yang
Age: 33
Assistant professor, University of Pennsylvania
Designs “smart” photonic devices for lightning-fast computers and communications networks. While at Bell Labs, she codeveloped a liquid microlens that can be electronically focused in milliseconds to direct light signals inside optical fibers.

Yuankai Zheng
Age: 34
Research scientist, Data Storage Institute (Singapore)
Simplified the production of magnetic RAM, making this fast, nonvolatile form of computer memory cheaper and more practical. A thumbnail-sized magnetic-RAM chip could store 32 gigabytes of data.