"Nanobiotechnologists" are imitating, harnessing, and probing nature at the level of the living cell.
The world's a stage, and nature is a splendid stage manager. Understanding how nature works and imitating nature at work are among the goals of nanobiotechnology.
Some 20% of the 75 "jump-start" user projects approved for ORNL's Center for Nanophase Materials Sciences are classified as nanobiotechnology. Dozens of Oak Ridge scientists are engaged in nanobiotechnology studies, cutting-edge research where materials, imaging, computational, and biological sciences merge.
Mitchell Dokycz, leader of biochemical and biophysics programs in ORNL's Life Sciences Division, defines nanobiotechnology in terms of the four types of projects in which his group is engaged. "We have used biological materials in innovative ways, such as training bacteria to light up when they sense a specific chemical," he says. "We have used synthetic materials in natural ways, copying nature's way of doing things. We have created devices that are hybrids of nanoscale and biological materials. Finally, we have used nanoscale probes to interrogate biological systems."
Michael L. Simpson, an ORNL-University of Tennessee joint faculty appointee and leader of the Nanobiological Materials Sciences Group in the Laboratory's Condensed Matter Sciences Division, says the types of users at the nanocenter will include researchers from the biomedical, fundamental biology, and biomimetics communities. They will pursue applications such as drug delivery, therapeutics, nanoscale electrochemical sensors, and advanced computation.
ORNL researchers and users at the nanocenter will have access to state-of-the-art instruments for nanobiotechnology research. "We will fabricate new nanostructures using an electron
beam writer and characterize them using microscopes, spectroscopy tools, and e-beam holography," Simpson says.
One grand challenge of nanobiotechnology, Doktycz says, is to understand what happens at the interfaces between living Wayand nonliving entities. Here are several examples.
Mengdawn Cheng of the Environmental Sciences Division has shown that 10-nanometer manufactured particles can do more damage to both human and mouse lung cells than micron-sized particles. Nanometer-sized particles emitted by aircraft and automotive vehicles contribute largely to smog found in the world's metropolitan areas.
ORNL Corporate Fellow Eli Greenbaum leads studies of the toxicities that arise at the interface between a microelectrode array and surviving retinal tissue in the typical eye of a legally blind person suffering from retinal degenerative disease.
ORNL Corporate Fellow Thomas Thundat and colleague Ming Su have used gold nanoparticle-labeled probe DNAs to amplify the mass change on Thundat's revolutionary microcantilevers so they bend more. In this way, a target DNA strand that binds with the probe DNA is more easily detected.
The research group of ORNL Corporate Fellow Tuan Vo-Dinh examines proteins in a living cell penetrated by a nanoscale optical fiber tipped with an antibody probe. The group has developed DNA probes based on silver nanoshells and nanoparticles that have detected the AIDS virus and a breast cancer gene by changing their surface-enhanced Raman scattering signals.
Timothy McKnight, Simpson, and their ORNL colleagues penetrate living cells in a checkerboard arrangement in a massively parallel fashion with thousands of vertically aligned carbon nanofibers tipped with plasmid-DNA. The genes in the injected DNA stimulate the cells to produce proteins encoded by the foreign genes. One of the expressed proteins is green fluorescent protein (GFP), which turns the cell green, visibly indicating gene expression in the cell-nanofiber hybrids.
UT and ORNL researchers, including Doktycz, Simpson, and McKnight, created a microarray biosensor using ink-jet technology to spit single droplets of cells into alternating tiny wells in a synthesized carbon nanofiber membrane. Each of the bacterial cells grown in the wells has a GFP gene coupled to a chemically sensitive promoter. When the sensor is exposed to that chemical, the promoter induces expression of the GFP gene, causing the cells to glow green.
One exciting "jump-start" nanobiotechnology project that involves Simpson, McKnight, and Gomez Wright of ORNL's Nuclear Science and Technology Division would fabricate a device that could create custom-tailored medical compounds faster than ever before. The project, which is being carried out in the nanocenter's clean room (see next article), is led by Joseph Matteo, founder and chief executive officer of the local research firm NanoTek. The company is building a small, microfluidic machine to synthesize quickly and reliably drugs and medicines tailored to individual patients' needs, as well as diagnostic imaging agents.
Matteo's device, which uses ORNL-developed technology to manipulate ions in a stream of solution, operates at high speed using low volumes of fluids. Potential commercial applications include short-order manufacture of drugs and other chemicals with a short shelf life; a better way to make short-lived radioactive compounds for medical diagnostic imaging technology, such as positron emission tomography; and bio-threat detection.
A primary function for this closed-loop, information-driven, serial discovery machine is to synthesize a drug, test the drug against a patient's fluids, feed the test results back to the synthesis process, and optimize the drug to get the desired improvement in patient health.
If the concept works, the findings could demonstrate the feasibility of "point of use" drug synthesis, ushering in a new era of personalized medicine, where patients visit doctors, undergo tests, and receive medicines formulated especially for them in minutes. The discovery, in turn, may speed up nature's way of healing the body.
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