SAN FRANCISCO (02/26/2004) - People pay good money for Quantum Dot Corp's products -- tiny semiconductors just about 10 nanometers across. To pharmaceutical companies, medical researchers, and diagnostic labs, these "quantum dots" are more valuable than precious metals. They buy small, brightly colored vials, priced from US$300 to $600, each containing trillions of the dots in solution -- enough for about 100 tests. Then they look at them.
The best thing about Quantum Dot's semiconductor crystals -- known as Qdot nanocrystals -- is that you can see them: inside cells, under a microscope, or in multiple colors under the same light, depending on their size and composition. They're brighter than fluorescent proteins and dyes, and remain lit much longer, according to Andy Watson, vice president of business development.
Qdots are being used for cell analysis, gene expression, and medical diagnostics. By studying the glowing crystals, which can bond with proteins, researchers can track those proteins to learn about cells in a sample. Other applications include analyzing the genetic makeup of cancer cells and determining how well a cancer drug binds its target.
Quantum Dot was founded in 1998 with licenses to discoveries by Moungi Bawendi at MIT and Paul Alivisatos of University of California at Berkeley. Those researchers discovered biological applications of quantum dots, which had been developed in the 1980s for use in physics research. The company has raised more than $37.5 million in financing so far, and the Forbes/Wolfe Nanotech Report recently named their technology one of the top breakthroughs of 2003.
Quantum Dot manufactures in a lab setting at the company's headquarters. When technicians combine cadmium and selenium in a solution and apply heat, the elements form semiconductor crystals. Modifying the process slightly can change the size and composition of the crystals so that they will glow in different colors. Zinc and sulfur are added to the mix, forming a shell around each crystal. Then the crystals are coated with molecules to create conjugates, which can hook up with proteins.
Companies such as Genentech Inc. have used Qdots to determine the concentration of substances in a sample, such as new cancer drugs that are supposed to target certain parts of cells. And researchers are attaching Qdots to single molecules to track their activity. One team used Qdots to study the behavior of glycine receptors in neurons.
Neurotransmitters travel from one neuron to another and then bond with receptors on a synapse. Observing the activity of those receptors in real time, the researchers found that they were very active, moving to different parts of a synapse, to other synapses, and to areas outside the synapses, says research scientist Maxime Dahan.
The miniature size and long-lasting lucidity of the Qdots allowed the scientists to record the activity of receptors in real time in live cultured neurons. Much larger probes would not have worked, as the receptors are only about 5 nanometers wide. "The motion of these receptors with the large probe on its back is going to be modified, and you don't get a real view of the natural motion," Dahan says. "Now we realize that these (receptors) ... are not stable at all -- they keep moving all the time." The discovery could lead to better drug design if researchers can determine how to change the number of receptors at a given synapse.
The success of Dahan and colleagues illustrates the potential of Qdots to study single molecules, especially for tracking multiple targets simultaneously, says Adam Douglass, a cell biologist at University of California at San Francisco.
A recent deal with Matsushita Electric Industrial Co. Ltd. has produced a device for studying samples treated with Qbead microspheres -- linked combinations of Qdot nanocrystals. As many as 200 uniquely coded microspheres with attached probes can be made from combinations of nanocrystals, so researchers can detect expression of 200 different genes in a sample. The system lets researchers study hundreds of genes in thousands of samples per day.
The microspheres are sensitive enough to detect as few as 100,000 molecules of RNA -- much more sensitive than microarrays -- according to Quantum Dot. Matsushita will make the device, called the Quantum Dot Mosaic Q100 Scanner.
The glowing crystals may also find their way into quick "strip" tests, similar to instant pregnancy tests, as a result of a partnership with the Jet Propulsion Laboratory at the California Institute of Technology. This technology could be used to test for substances associated with heart conditions and prostate cancer, Watson says.
Qdots can show not only whether a substance exists in a sample but how much of it is there. Eventually, Qdots could end up in inexpensive, over-the-counter test kits. That would be a big future for a very small product.
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