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Harvard Team Wins $380K NSF Grant to Develop Microfluidic Cell-Based Assay

An investigator at Harvard University has won a $380,000 grant from the National Science Foundation to develop a microfluidics-based fluorescent-activated device that will incorporate the single-droplet control of microfluidics with the cell screening and sorting of conventional FACS.
The device encapsulates single cells in droplets of a biocompatible, fluorinated oil, rather than air, so that the cells can be interrogated with a laser, David Weitz, principal investigator on the grant, told CBA News recently.   
Called M-FACS, the technology could enable researchers to obtain robust data on a distribution of a population of cells.
“If we want, we can merge with that drop another drop that contains nutrients, reagents, or a drug, or anything like that,” said Weitz, who is also a professor of physics and applied physics at Harvard.
The cells, which are enclosed in an isolated picoliter-scale environment, can be placed in an incubator to grow, and if they excrete a chemical, such as an antibody, the chemical’s concentration in the drop can be grown to very high levels within a short period, he said.
“We can add something that does, for example, an in situ enzyme-linked immunosorbent assay in the drop, and then we can sort the drops based on the results of that assay,” said Weitz.
The cells are sorted based on criteria the researchers choose, which could include chemicals excreted by the cells or presented on their surface, as well as cell growth, said Weitz. He explained that they can sort the results on a scale of 1,000 to 10,000 cells per second, which is close to the sorting rate of most FACS machines.
Weitz said that with conventional FACS, a population of cells is focused into a stream, probed with a laser, put into drops, and then immediately sorted based on what the laser has probed.
“This technique has two disadvantages, from our perspective,” he said. First, “you have to sort the cells as soon as you put them into drops. In addition, you are making an aerosol, so if you are using dangerous cells, you have to do it under really contained conditions.” 
By comparison, M-FACS can qualitatively change the applicability of the FACS technique so that cells can be used as a part of the assay itself and tested against a library of compounds, and sorted based on the results.
Weitz said he and his group are still trying to perfect some of the detection schemes. “We are essentially doing in situ detection of excreted molecules,” he said. “We are trying to develop a fairly general detection scheme.”  
Weitz said he recently filed a patent application for the technology, and is also preparing several manuscripts for peer-reviewed publication. He said his team is currently preparing its first publication, which shows that the device can have sensitive cells remain viable in the drops. A second publication will focus on demonstrating that they can sort them based on fluorescence and fluorescent probes.

“If we want, we can merge with that drop another drop that contains nutrients, reagents, or a drug, or anything…”

“We are also working on perfecting various in situ assays, such as ELISA assays, which will allow us to demonstrate that if the cells can excrete a chemical, we can detect that chemical,” said Weitz. “I would hope that we can finish that within the next six months.”
The grant began on Sept. 1, 2007, and runs for three years. “Hopefully, within the next seven months, we’ll have at least three more publications,” Weitz said.
He went on to say that he and his group have already completed 75 percent of their initial goals, and in the remaining two years of the grant, the group will develop strategies to make everything work as one unit.
Weitz said that RainDance Technologies, a company spun out of his lab in 2004, will commercialize at least part of the M-FACS technology (see CBA News 1/12/07 and CBA News 5/4/07).
“Some of what we do will go directly to RainDance, and some things we may commercialize separately,” he added.
Weitz, a RainDance director, said that the company has commercialized virtually all of the IP that has been developed in his lab, including most of the droplet technology. The decision to commercialize the M-FACS technology is more or less up to the RainDance management, he said. 
“If there is an opportunity for commercialization, we’ll do it either through RainDance if they are interested, or if not, through another company,” said Weitz.
RainDance, which also counts as directors Curagen and 454 Life Sciences founder Jonathan Rothberg, former Affymetrix president Sue Siegel, and former Applied Biosystems president Michael Hunkapiller, currently has several applications in mind for the launch of its instrument, Weitz said.
He pointed out that RainDance’s core technology, the NanoReactor Chip, can be modified to use M-FACS for cell-based applications.

“We are doing the preliminary development necessary to do that,” said Weitz. “We have different detection schemes, different assays involved, et cetera.”

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