Microfludic chip solves riddle of cell density

The new technology could enable researchers to gain biophysical insight into fundamental cellular processes such as adaptations for survival. The new method is described in the Proceedings of the National Academy of Sciences and involves measuring the buoyant mass of each cell in two fluids of different densities. William Grover, a research associate in MIT's Department of Biological Engineering, said: "Density is such a fundamental, basic property of everything. 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 breakthrough is based on an adaptation an existing technique devised to measure the buoyant mass of single living cells. The 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 cantilver vibrates within a vacuum; when a cell flows through the channel, the frequency of a cantilever's vibration changes. The cell's buoyant mass (its mass as it floats in fluid) can then 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 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, according to the researchers, the entire measurement process for one cell takes as little as five seconds. The researchers tested their system with several types of cells, including red blood cells and leukemia cells. In the leukemia study, cells were treated with an antibiotic called staurosporine, then measured the density less than an hour later. Normally, a change would be difficult to detect, but the highly sensitive device revealed a clear change in density. With such a rapid response and sensitivity, the method could become a useful way to screen potential cancer drugs. Grover, MIT PhD recipient, Andrea Bryan and Scott Manalis, a professor of biological engineering, are now investigating the densities of other types of cells. The team is starting to work on measuring single cells as they grow over time — specifically cancer cells, which are characterised by uncontrolled growth. Manalis said: "Understanding how density of individual cancer cells relates to malignant progression could provide fundamental insights into the underlying cellular processes, as well as lead to clinical strategies for treating patients in situations where molecular markers don't yet exist - or are difficult to measure due to limited sample volumes."