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Abstract
Electrical correlates of the physiological state of a cell, such as membrane conductance and capacitance, as well as cytoplasm conductivity, contain vital information about cellular function, ion transport across the membrane, and propagation of electrical signals. They are, however, difficult to measure; gold-standard techniques are typically unable to measure more than a few cells per day, making widespread adoption difficult and limiting statistical reproducibility. We have developed a dielectrophoretic platform using a disposable 3D electrode geometry that accurately (r2 > 0.99) measures mean electrical properties of populations of ~20,000 cells, by taking parallel ensemble measurements of cells at 20 frequencies up to 45 MHz, in (typically) ten seconds. This allows acquisition of ultra-high-resolution (100-point) DEP spectra in under two minutes. Data acquired from a wide range of cells – from platelets to large cardiac cells - benchmark well with patch-clamp-data. These advantages are collectively demonstrated in a longitudinal (same-animal) study of rapidly-changing phenomena such as ultradian (2–3 hour) rhythmicity in whole blood samples of the common vole (Microtus arvalis), taken from 10 µl tail-nick blood samples and avoiding sacrifice of the animal that is typically required in these studies.
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Details
1 Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, Surrey, UK; Department of Electrical Engineering and Electronics, University of Liverpool, Brownlow Hill, Liverpool, UK
2 Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, Surrey, UK; Department of Engineering, Wake Forest University, Wake Downtown, Winston-Salem, USA
3 Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, Surrey, UK
4 School of Biosciences and Medicine, University of Surrey, Guildford, Surrey, UK
5 Department of Biomedical Engineering, Faculty of Engineering, The Hashemite University, Zarqa, Jordan
6 Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, Surrey, UK; MRC Laboratory for Molecular Biology, Francis Crick Avenue, Cambridge, UK
7 School of Biosciences and Medicine, University of Surrey, Guildford, Surrey, UK; School of Physiology, Pharmacology & Neuroscience, University of Bristol, University Walk, Bristol, UK