Dec. 11, 2002 — Scientists say they have conquered technical challenges that have stymied attempts to put quantum dots to work in biological imaging.
A trio of recent publications herald new achievements in using the inorganic fluorescent probes to shed light on cellular processes that have until now been viewed only briefly and dimly with the aid of organic dyes.
A publication in Science and two released online in Nature Biotechnology say quantum dot technology is ready to pay off on promises that it can be used to image multiple proteins and structures inside cells. Research results indicate that quantum dots are brighter, longer-lasting, more specific biomarkers than the organic dyes currently in use.
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“This is fascinating,” said Tom Petzinger, chief executive of Bioplex Corp., which is working on technology to aggregate quantum dots in beads, and on other biomedical uses of the semiconductor nanocrystals. Evidence that the nanoparticles did not distort the processes of living cells even after more than a week’s observation was particularly important to advancing the state of the science, Petzinger said..
Bioplex, owned in part by Pittsburgh’s LaunchCyte incubator, is one of only a few companies known to be working on quantum dot technology. Another, Quantum Dot Corp. of Hayward, Calif., is behind one of the Nature Biotechnology papers, along with Genentech Inc., the South San Francisco biotech powerhouse.
Just weeks before the paper came out, Quantum Dot launched its first nano-biotech product, the Qdot 605 Streptavidin Conjugate, semiconductor nanocrystals attached to a specific biomolecule for use in cell and tissue analysis.
“Before, the potential for quantum dots to label specific targets inside cells was a concept, but it had never been demonstrated,” said Quantum Dot scientist Xingyong Wu. “We showed that we actually can do it. Right now it can be used in real applications.”
Early attempts to label cellular targets linked quantum dots to biotin or the protein transferrin. Results were unsatisfactory: the labeling signal was weak and targeting was not as specific as testers hoped.
Wu and other Quantum Dot researchers, working with scientists from Genentech, resolved problems in surface coating and successfully labeled a number of targets. Quantum dots selectively and distinctly illuminated the breast cancer marker Her2, nuclear antigens and other subcellular structures in their research.
Quantum Dot plans to have three or four more products on the market within months, Wu said.
Academic and military scientists formed the team for the second Nature Biotechnology article. They were on a mission to refine quantum dot technology to make it generally available and workable in a broad range of uses. They succeeded, according to a researcher.
“The technique that we have developed is ready to use,” said Sanford M. Simon of Rockefeller University in New York. Working with the U.S. Naval Research Laboratory, Rockefeller scientists induced living cells to assimilate quantum dots, then tracked the marked cells for more than a week.
Their techniques for selectively and noninvasively tagging living cells using the semiconductor dots were designed with an eye to general use.
“The applications are all over the map in biology,” Simon said.
As promised, the inorganic fluorophores that are quantum dots held their fluorescence longer and burned more brightly than their organic dye counterparts in the Rockefeller/Navy experiments. Susceptible to more fine-tuning than organic dyes, the dots selectively labeled different proteins with different colors.
More than a week’s observation revealed no sign that the quantum dots affected cell processes, either. Marked cells grew, developed and signaled as usual, meaning the quantum dots could literally shed light on the processes of life at the subcellular level without influencing it.
“The paper is in a form that makes it possible for anyone to use the techniques,” said investigator Jyoti K. Jaiswal, also of Rockefeller. Prior to this work, imaging technology would only allow brief, indistinct glimpses of crude cellular interaction, he explained. Now scientists can watch a number of different processes at once by way of quantum dot enhanced live cell imaging, he said.
“We know cells move around, talk to each other, interact, and in some sense influence each other,” Jaiswal said. “We don’t understand how these interactions come about. For that purpose we have to monitor the cells in real time, watch them as the interaction goes on.”
A third team of researchers reported their solution to the biocompatibility problem in Science. They sheathed the dots in phospholipid membranes and hooked them to DNA to produce clear images in growing embryos, where the nanocrystals appeared stable and nontoxic.
“These three papers combined indicate that bioconjugate nanocrystals will have major applications in biology and medicine,” said Shuming Nie, director of nanotechnology at Emory University’s Winship Cancer Institute.
Nie also serves as senior science consultant to Bioplex, which licensed nanobead technology he had developed. Dots aggregated into beads are encoded to enhance multiplexing capabilities, expanding the potential for tagging multiple targets simultaneously.