A microfluidic device capable of continuous quantification of single-cell specific membrane capacitance and cytoplasm conductivity

Abstract

This paper presents a microfluidic system enabling continuous characterization of specific membrane capacitance (C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">specific membrane</sub> ) and cytoplasm conductivity (σ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">cytoplasm</sub> ) of single cells by aspirating cells continuously through a constriction channel with cell elongations and impedance profiles at two frequencies (1 kHz and 100 kHz) measured simultaneously. 1 kHz impedance data were used to evaluate cellular sealing properties and 100 kHz impedance data were used to quantify membrane capacitance and cytoplasm conductance, which were than translated to C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">specific membrane</sub> and σ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">cytoplasm</sub> based on the proposed equivalent circuit model. Four cell lines were used to evaluate this technique, producing C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">specific membrane</sub> and σ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">cytoplasm</sub> of 3.81±0.90 μF/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and 0.49±0.07 S/m (CRL-5803, n=489), 4.28±1.05 μF/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and 0.45±0.08 S/m (CCL-185, n=487), 3.67±1.00 μF/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and 0.47±0.09 S/m (CRL-1932, n=302), as well as 4.53±1.51 μF/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and 0.55±0.14 S/m (CRL-1999, n=216), respectively.