Microfluidic measurement of individual cell membrane water permeability

Highlights: • We calibrated and validated lab-on-chip dynamic cell sizing and cell membrane permeability measurements in individual cells. • Volume-correlated impedance change of myriad individual yeast cells was rapidly measured after mixing with anisosmotic media. • Measurements were performed within 0.26 s after mixing with media from separate inlets at up to 10 electrodes over 1.3 s. This paper reports a microfluidic lab-on-chip for dynamic particle sizing and real time individual cell membrane permeability measurements. To achieve this, the device measures the impedance change of individual cells or particles at up to ten time points after mixing with different media, e.g. dimethyl sulfoxide or DI water, from separate inlets. These measurements are enabled by ten gold electrode pairs spread across a 20 mm long microchannel. The device measures impedance values within 0.26 s after mixing with other media, has a detection throughput of 150 samples/second, measures impedance values at all ten electrodes at this rate, and allows tracking of individual cell volume changes caused by cell osmosis in anisosmotic fluids over a 1.3 s postmixing timespan, facilitating accurate individual cell estimates of water permeability. The design and testing were performed using yeast cells (Saccharomyces cerevisiae). The relationship between volume and impedance in both polystyrene calibration beads as well as the volume-osmolality relationship in yeast were demonstrated. Moreover, we present the first noninvasive and non-optically-based water permeability measurements in individual cells.