More than 2,000 years after Archimedes found a way to determine the density of a king’s crown by measuring its mass in fluids, MIT scientists have used a similar principle to solve an equally vexing puzzle — how to measure the density of a single cell.
“Density is such a fundamental, basic property of everything,” says William Grover, a research associate in MIT’s Department of Biological Engineering. “Every cell in your body has a density, and if you can measure it accurately enough, it opens a whole new window on the biology of that cell.”
The new method, described in the Proceedings of the National Academy of Sciences the week of June 20, involves measuring the buoyant mass of each cell in two fluids of different densities. Just as measuring the crown’s density helped Archimedes determine whether it was made of pure gold, measuring cell density could allow researchers to gain biophysical insight into fundamental cellular processes such as adaptations for survival, and might also be useful for identifying diseased cells, according to the authors.
Grover and recent MIT PhD recipient Andrea Bryan are lead authors of the paper. Both work in the lab of Scott Manalis, a professor of biological engineering, member of the David H. Koch Institute for Integrative Cancer Research and senior author of the paper.
Measuring the density of living cells is tricky because it requires a tool that can weigh cells in their native fluid environment, to keep them alive, and a method to measure each cell in two different fluids.
In 2007, Manalis and his students developed the first technique to measure the buoyant mass of single living cells. Their device, known as a suspended microchannel resonator, pumps cells, in fluid, through a microchannel that runs across a tiny silicon cantilever, or diving-board structure. That cantilever vibrates within a vacuum; when a cell flows through the channel, the frequency of the cantilever’s vibration changes. The cell’s buoyant mass can be calculated from the change in frequency.
To adapt the system to measure density, the researchers needed to flow each cell through the channel twice, each time in a different fluid. A cell’s buoyant mass (its mass as it floats in fluid) depends on its absolute mass and volume, so by measuring two different buoyant masses for a cell, its mass, volume and density can be calculated.
The new device rapidly exchanges the fluids in the channel without harming the cell, and the entire measurement process for one cell takes as little as five seconds.
David Weitz, professor of physics at Harvard University, says the new technique is a clever way of measuring cell density, and opens up many new avenues of research. “The very interesting thing they show is that density seems to have a more sensitive change than some of the more standard measurements. Why is that? I don’t know. But the fact that I don’t know means it’s interesting,” he says.