Background: The microfabricated impedance spectroscopy flow cytometer used in this study permits rapid dielectric characterization of a cell population with a simple microfluidic channel. Impedance measurements over a wide frequency range provide information on cell size, membrane capacitance, and cytoplasm conductivity as a function of frequency. The amplitude, opacity, and phase information can be used for discrimination between different cell populations without the use of cell markers.Methods: Polystyrene beads, red blood cells (RBCs), ghosts, and RBCs fixed in glutaraldehyde were passed through a microfabricated flow cytometer and measured individually by using two simultaneously applied discrete frequencies. The cells were characterized at 1,000 per minute in the frequency range of 350 kHz to 20 MHz.Results: Cell size was easily measured with submicron accuracy. Polystyrene beads and RBCs were differentiated using opacity. RBCs and ghosts were differentiated using phase information, whereas RBCs and fixed RBCs were differentiated using opacity. RBCs fixed using increasing concentrations of glutaraldehyde showed increasing opacity. This increased opacity was linked to decreased cytoplasm conductivity and decreased membrane capacitance, both resulting from protein cross‐linking.Conclusions: This work presents label‐free differentiation of cells in an on‐chip flow cytometer based on impedance spectroscopy, which will be a powerful tool for cell characterization.
: Purpose: Assessment on enucleated pig eyes of a novel and minimally invasive method for the continuous monitoring of intraocular pressure (IOP), based on a novel wireless contact lens sensor (CLS).Methods: The wireless CLS is a disposable silicone soft contact lens with a sensor embedded in it, allowing the wireless measurement of changes in corneal curvature induced by IOP variations. A CLS was adapted and tested on enucleated pig eyes. To demonstrate the measurement principle of the device, the enucleated pig eye was cannulated, allowing precise control of IOP. The CLS signal was then compared to the imposed IOP.Results: First, the IOP of enucleated pig eyes was changed between 11 and 14 mmHg, simulating ocular pulsation. Then, IOP was changed with static steps of 1 mmHg between 20 and 30 mmHg to assess the reproducibility and linearity of the CLS. In both cases, measurements from the CLS and IOP showed very good correlation. A calibration graph shows that the CLS is capable of monitoring the IOP of each individual eye with a reproducibility of ± 0.2 mmHg (95% confidence interval).Conclusion: The wireless CLS shows a good functionality to monitor the IOP on enucleated pig eyes. The device is placed in the same way as a soft disposable contact lens. This device would allow a minimally invasive and continuous monitoring of IOP over prolonged periods of up to 24 hr, regardless of patient activity, thus opening up new diagnostic and therapeutic methods to manage glaucoma.
A model showing the importance of the parameters characterizing ion transport through geometrically defined nanoslits filled with electrolyte is presented. A conductance plateau (in log-log scale) at low salt concentrations in the nanometer-sized apertures was both modeled and measured. This is due to the dominance of the effective surface charge density in the nanoslits inducing an excess of mobile counterions to maintain electroneutrality. The nanoslit conductance could be regulated at low salt concentrations by adjustment and by an external voltage applied on the chip. This effect can be exploited for ionic flow regulation in nanofluidic devices.
The poor efficiency of microfluidic single cell trapping is currently restricting the full potential of state-of-the-art single cell analyses. Using fluid dynamics simulations in combination with particle image velocimetry to systematically optimize trap architectures, we present a microfluidic chip with enhanced single cell trapping and on-chip culture performance. Upon optimization of trap geometries, we measured trapping efficiencies of up to 97%. Our device also enables the stable, relatively long-term culture of individual non-adherent mammalian cells in high-throughput without a significant decrease in cell viability. As a first application of this platform we demonstrate the automated separation of the two daughter cells generated upon single cell division. The reliable trapping and re-trapping of mammalian cells should for example provide the fundament for novel types of investigations in stem cell and tumour cell biology, which depend on reliable tracking of genealogical relationships such as in stem cell lineage tracking.