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Nanoscience Made Easy

The advance of engineering at extremely small scales has led to marvels of manufacturing, producing tiny transistors and circuits so close-packed that palm-sized devices now have the computing power and memory once held by room-sized machines. But two things this technology is not: Simple and cheap. What Intel can manage, a typical biologist cannot. Scientists studying the basic processes of life need equipment of a different kind, not so sophisticated but much easier to use.

Harvard’s Kavli Institute for Bionano Science and Technology has its own idea of the cutting edge: tools for the non-expert.

You could call it nanotechnology for the rest of us, and it is central to the mission of the Kavli Institute for Bionano Science and Technology (KIBST) at Harvard University. As the Institute’s co-director, physicist David Weitz, explains, “We want to develop tools that can be used by everybody - particularly non-experts - that incorporate nanoscience and impact biology in a way that is accessible.” Rather than simply advancing nanotech to smaller and smaller scales, KIBST aims to make it practical for as many people as possible.

Illustration of a microcircuit integrated in fabric

To show how flexible materials can be used to integrated microcircuits into fabrics, Adam Siegel and colleagues at Harvard University, including Kavli Institute co-director George Whitesides, invented a structure 200 micrometers wide capable of being tied into a knot. Depending on the solder compositions the wire can be solid or flexible, and any breaks can be healed by reheating it. (Credit: Adam C. Siegel and George Whitesides / Harvard)

Making Cheaper, Simpler Technology

As an example, Weitz points to the work of KIBST’s other co-director, George M. Whitesides, a Harvard professor of Chemistry and Chemical Biology. Whitesides pioneered soft lithography, which makes nanoscale structures by molding, etching or stamping with flexible materials. This technology does not have the same precision as traditional nanolithography used to make most semiconductors, but it is cheaper and can do some things that conventional methods cannot, such as creating structures on curved surfaces. (The most common nanolithography method is to etch complex geometric patterns on flat surfaces by shining light through a photomask).

Among other things, soft lithography does not require the completely dust-free conditions needed to make semiconductors. “What I call a ‘dirty clean room’ is enough,” says Weitz, a Harvard professor of Physics and Applied Physics whose research is focused on fluids, gels and other soft materials and play key roles in cellular biology. This is “a room where you keep it as clean as you can and you have all the filters, but you don’t try to keep every last bit of dust out.” Soft litho is faster, too. A microfluidics device, used for sorting cells, can take two weeks to produce with traditional methods “if things really go well,” says Weitz. At Harvard, soft lithography has reduced the turnaround time to two days - one day for printing a mask at a West Coast facility and one day to express-ship the mask to Cambridge.

Since its introduction in the early-1990s, soft lithography has been a boon to researchers in academia and industry. It’s not designed to produce the next generation of microprocessors, but it’s ideal for scientists who need tools for biological and medical research tasks, such as identifying and isolating cancer cells. As such, it’s a model for the research and technology development that Weitz and Whitesides are now encouraging at KIBST, which was founded in 2006 and began its recruiting and solicitation for project proposals in 2007. What they look for are ideas that could affect biological research much as soft litho has. They want research that has real-world impact – even commercial success – whether or not it garners traditional academic rewards such as prizes and published papers.

Looking for Promise and Potential

Photo of a double-bubble delivery system

Researchers led by David Weitz, co-director of the Kavli Institute for Bionano Science at Harvard University, have developed a “double bubble” method of delivering substances such as cancer drugs to locations where they would not survive without protection. A double-emulsion drop snaps off from a jet of two fluids within an outer fluid of viscous silicon oil. The middle fluid is water that contains a surfactant called sodium dodecyl sulfate, or SDS. The inner fluid is silicon oil. (Credit: Andrew Shinichi Utada / Harvard)

Toward that end, they look for proposals that, in Whitesides’ words, “don’t peer-review well” but promise potentially big payoffs. Weitz explains: “What peer-reviews well is something that falls within the traditional disciplines, is not very risky, has a clear, very well-defined outcome and a high probability for success.” He and Whitesides are willing to take chances on projects that may have a very low probability for success but, if they work, “will be spectacular.”

The first round of proposals was solicited in 2007, and over twenty proposals were received. Four inaugural grants of the KIBST were awarded to six Harvard faculty. They include both experienced senior faculty members as well as junior faculty just beginning their research careers. A second round of proposals will be solicited in the coming months.

The target of all this technology, including tools now in use as well as those yet to be invented, is life at the molecular level. “Most of what happens in biology happens at the scale of ten to 1,000 nanometers,” says Weitz. The mission of KIBST is to draw on the work of Harvard researchers to illuminate the nanoscale realm where the physical sciences and biological science meet. One example is the new science of proteomics, the study of the proteins and their functions. It’s a realm where disciplines meet. “Everything becomes structure,” Weitz says, when life is observed at the nanometer scale and scientists study “the chemical motors that drive biologic processes.” At this interface of biology, chemistry and physics, KIBST is developing the tools and techniques that can be used by scientists from all those disciplines.