An MIT researcher has come up with a microfluidic chip that automatically analyzes a common model organism.
The phrase “lab on a chip” usually conjures up images of rapid diagnostic tests. But for Mehmet Yanik, MIT assistant professor of electrical engineering and computer science, it means something different: thousands of microscopic nematode worms circulating on a chip only a few millimeters thick.
The technology promises to automate and speed up the slow and tedious process of genetically screening thousands of C. elegans worms, a popular model organism. This practice, which is standard practice in many labs studying gene function, can take months or even years. The worm-analyzing chips work “orders of magnitude faster,” says Yanik. “This technology will allow genome-wide screens at subcellular resolution in less than a day.” For this idea, Yanik won a 2007 Innovator Award from the National Institutes of Health, which will provide the project with $2.5 million over the next five years.
A geneticist’s best friend
C. elegans is often used in research because of its small size (less than 1 millimeter in length), transparency to visible light, and easy-to-manipulate genetics. Researchers use them to figure out which genes are involved in physiological processes, such as the development of neurons.
Typically, in such experiments, worms are exposed to a chemical that randomly mutates the genes in their eggs, resulting in offspring with physical changes. Researchers then examine each individual offspring for these changes. When they find a worm with the change of interest, they analyze its genome to determine which gene or genes were mutated, allowing them to link the genes with specific physiological processes. To conduct this kind of screen at the genome-wide level or to look at more than one physiological process requires the analysis of 20,000 to 40,000 animals.
Worms in circulation
Yanik’s chip is based on microfluidic technology: fluid is pumped through a network of 10 to 500 micron-wide channels etched into a chip that is only a couple of millimeters thick. The chip is made from a transparent plastic-like polymer.
This diagram shows the flow of C. elegans through a microfluidic chip developed by MIT’s Mehmet Yanik. (Image courtesy Mehmet Yanik, MIT)
Worms are fed into the chip through an inlet and continuously recirculated. Low-pressure suction immobilizes one worm in a chamber, while the others are flushed out and sent back into circulation. The immobilized worm is imaged through the transparent chip by a white-light or fluorescence microscope. The technology is so precise that worms can be imaged at the subcellular level. Once imaged, the worms are sent to either a multi-well plate for genetic analysis or to collection chambers located on another chip, where they can be monitored or exposed to drugs or other compounds.
“With traditional screens, you have to examine each animal visually, which introduces human error,” says Yanik. “It’s somewhat subjective and quite slow. With this technology, we can program a computer to analyze the images as they come through, and we can let the computer determine which animals should be kept for further analysis.”
Yanik’s group now plans to use its “lab on a chip” technology to study the genetics of neural degeneration and regeneration after injury.
He is also collaborating with Richard Nass, an assistant professor of pediatrics and pharmacology at Vanderbilt University Medical Center. Nass’s group would like to use the chip technology to find genes involved in the development of Parkinson’s disease. “The chip will allow the screening of thousands of compounds for their effect on worm behavior or their neuroprotective properties,” more quickly than conventional technology by orders of magnitude, says Nass.