Method to Rapidly Measure Cell Density Developed

Measuring the density of individual cells can provide important information about their physiological state, such as proliferation, differentiation, or death. Changes in cell density occur as cells gain or lose water and molecules, but tracking these changes at single-cell resolution and large scale has been challenging. Now, researchers at MIT have developed a method to measure cell density quickly and accurately, analyzing up to 30,000 cells per hour.

The team, led by Scott Manalis, built on previous work with a microfluidic device called the suspended microchannel resonator (SMR), which measures the mass of cells by detecting changes in vibration frequency as cells pass through a silicon cantilever. In earlier adaptations, cells were passed through the device twice in fluids of different densities to calculate mass, volume, and density, but this process was slow and limited throughput.

To improve speed, the researchers combined the SMR with a fluorescent microscope. Cells are suspended in a fluorescent dye that is not absorbed by the cells. As cells flow past the microscope, a drop in fluorescence reveals cell volume, followed by mass measurement in the resonator. This streamlined process enables rapid density calculation without sacrificing precision.

The method was used to study T cells as they become activated. Activated T cells were found to gain water faster than other molecules, resulting in a drop in density from 1.08 to 1.06 grams per milliliter. According to Weida Wu, first author of the study published in Nature Biomedical Engineering, “These data are pointing to the notion that cell density is an interesting biomarker that is changing during T-cell activation and may have functional relevance to how well the T cells could proliferate.”

The approach also showed that density changes can predict how tumor cells respond to cancer drugs. Preliminary studies found that combining mass and density measurements improves prediction accuracy for drug response in both immune and tumor cells. The researchers are now exploring applications in evaluating cell fitness for therapeutic protein production.