Wednesday, May 02, 2007

Weighing Living Cells

An ultrasensitive method for weighing cells could lead to a cheap and easy-to-use diagnostic device.

By Michael Patrick Gibson

Cell counter: In this experimental biodetector made at MIT, cells flow through a U-shaped microchannel in a cantilever. As the cells travel through the cantilever, their added mass alters the speed at which the cantilever vibrates, allowing the cells’ mass to be measured. Credit: Thomas Burg

Researchers at MIT have demonstrated that an extremely sensitive biomolecule detector can measure the weight of single living cells. The new biodetector, which the researchers described in the journal Nature, could provide, among other applications, a practical and cheap way to count particular types of cells in, say, a blood sample. (See "Demo: Sensing Success.")

The heart of the detector is a tiny, vibrating, silicon slab, or cantilever. Inside it, a U-shaped microchannel allows fluids containing cells to flow. As cells travel through the cantilever, their added mass alters the speed at which the cantilever vibrates. "We demonstrated a totally new method for measuring the mass of cells or nanoparticles in solution," says Scott Manalis, a professor of biological and mechanical engineering at MIT.

The new device could allow medical researchers and physicians to avoid the use of expensive and fragile optic readers when determining the concentrations of specific types of cells in a sample. For example, the number of CD4 cells is an indicator of the immune system's health in AIDS patients. To count such cells, researchers currently use an optic-based detector. First, they attach fluorescently labeled antibodies to the target cells. When the fluorescently tagged cells flow through a channel, an optical detector images them, allowing researchers to measure the quantity.

Instead of labeling the targeted cells with fluorescent antibodies, Manalis and colleagues plan to use nanoparticles. "The same approach can be used for detection by mass," says Manalis, "except the fluorescent molecule would be replaced by a nanoparticle. Instead of making specific cells brighter, they can be made heavier so they stand out from the background."

"It's a nice nonoptical way to do detection," says Stephen Quake, a professor of biological engineering at Stanford University. Quake says that the method could be particularly useful for applications that require small and portable devices. And he says that although more work is necessary to determine the best possible use of the detection method, the "research is promising enough that I'm very exited about it."

The MIT detector overcame several problems associated with existing devices for mass measurements. Typically, molecules to be weighed are placed on top of a cantilever: their added mass changes the speed of the cantilever's vibrating--just as it would in Manalis's method. But in existing methods, the measurements must be performed in a vacuum, so the devices are unable to measure living cells in a blood sample.

Manalis's team surmounts this limitation by pumping a fluid sample containing targeted cells through a microchannel hollowed out of the cantilever. Since the fluid of the sample is inside the cantilever, it does nothing to dissipate its vibrations in a vacuum. The method is sensitive enough to measure the weight of a single cell as it transiently flows through the channel.

A diagnostic device using Manalis's method for weighing mass could potentially be cheaper and more robust than one that employs optical detection. "Ultimately, we hope to have a disposable MEMS chip that would cost less than ten dollars and still give us the same diagnostic information that a more elaborate optical system could tell us," Manalis says.