Single-cell mass-density measurements using microchannel gradient centrifugation

We present a microchannel-based adaptation of mass density-gradient centrifugation for the mass density measurement of cells or microparticles. The workflow consists of three basic steps: Microchannel filling, centrifugation, and microscopy. Microchannel filling and subsequent centrifugation of two liquids with different densities allows the instantaneous, precise, and repeatable generation of a one-dimensional mass-density gradient and the simultaneous sedimentation of cells or particles of interest to a point where their mass density is equal to the gradient's mass density. We introduce two different methods, calibration particles and tracer molecules, for microscopic mass density readout. We demonstrate the measurement principle by measuring the mass density of yeast cells and show that the method allows the mass density measurement of single cells with a position dependent median uncertainty of 3.3 [Formula: see text] with a throughput of approximately 16000 cells per hour. This measurement precision is in the range of the best single-cell methods currently in use but with a higher throughput. The method is technically straightforward, robust, and affordable, making single-cell mass density measurements widely available.