Measuring single-cell density

• Main Authors: Grover, William H. (Contributor), Bryan, Andrea Kristine (Contributor), Diez Silva, Monica (Contributor), Suresh, Subra (Contributor), Higgins, John M. (Author), Manalis, Scott R. (Contributor)
• Other Authors: Harvard University- (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Materials Science and Engineering (Contributor), Massachusetts Institute of Technology. Department of Mechanical Engineering (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: National Academy of Sciences (U.S.), 2012-03-14T20:43:08Z.
• Subjects: Article
• Online Access: Get fulltext

We have used a microfluidic mass sensor to measure the density of single living cells. By weighing each cell in two fluids of different densities, our technique measures the single-cell mass, volume, and density of approximately 500 cells per hour with a density precision of 0.001 g mL-1. We observe that the intrinsic cell-to-cell variation in density is nearly 100-fold smaller than the mass or volume variation. As a result, we can measure changes in cell density indicative of cellular processes that would be otherwise undetectable by mass or volume measurements. Here, we demonstrate this with four examples: identifying Plasmodium falciparum malaria-infected erythrocytes in a culture, distinguishing transfused blood cells from a patient's own blood, identifying irreversibly sickled cells in a sickle cell patient, and identifying leukemia cells in the early stages of responding to a drug treatment. These demonstrations suggest that the ability to measure single-cell density will provide valuable insights into cell state for a wide range of biological processes.
EUREKA (Exceptional, Unconventional Research Enabling Knowledge Acceleration (R01GM085457))
National Institutes of Health (U.S.) (NIH Cell Decision Process Center Grant (P50GM68762))
United States. Army Research Office (Institute for Collaborative Biotechnologies Grant (W911NF-09-D-0001))
Massachusetts Institute of Technology (Whitaker Health Sciences Graduate Fellowship)
National Institutes of Health (U.S.) (Grant R01HL094270)
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant DK083242)