title: Measuring single-cell density.
abstract: 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.
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Grover
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Bryan
authors.forename: Monica
authors.initials: M
authors.lastname: Diez-Silva
authors.forename: Subra
authors.initials: S
authors.lastname: Suresh
authors.forename: John M
authors.initials: JM
authors.lastname: Higgins
authors.forename: Scott R
authors.initials: SR
authors.lastname: Manalis
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood; D000818:Animals; D001803:Blood Transfusion; D002452:Cell Count / Q000295:instrumentation* / Q000379:methods*; D048429:Cell Size; D004912:Erythrocytes / Q000166:cytology / Q000469:parasitology; D004913:Erythrocytes, Abnormal / Q000473:pathology; D006801:Humans; D007939:Leukemia L1210 / Q000097:blood / Q000188:drug therapy; D016778:Malaria, Falciparum / Q000097:blood / Q000469:parasitology; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods