Abstract
This paper presents a microfluidics-based approach capable of continuously characterizing instantaneous Young's modulus (Einstantaneous) and specific membrane capacitance (Cspecific membrane) of suspended single cells. In this method, cells were aspirated through a constriction channel while the cellular entry process into the constriction channel was recorded using a high speed camera and the impedance profiles at two frequencies (1 kHz and 100 kHz) were simultaneously measured by a lock-in amplifier. Numerical simulations were conducted to model cellular entry process into the constriction channel, focusing on two key parameters: instantaneous aspiration length (Linstantaneous) and transitional aspiration length (Ltransitional), which was further translated to Einstantaneous. An equivalent distribution circuit model for a cell travelling in the constriction channel was used to determine Cspecific membrane. A non-small-cell lung cancer cell line 95C (n = 354) was used to evaluate this technique, producing Einstantaneous of 2.96 ± 0.40 kPa and Cspecific membrane of 1.59 ± 0.28 μF/cm2. As a platform for continuous and simultaneous characterization of cellular Einstantaneous and Cspecific membrane, this approach can facilitate a more comprehensive understanding of cellular biophysical properties.
Highlights
Mechanical properties of the cytoskeleton (Einstantaneous and Eequilibrium) and electrical properties of cell membrane (Cspecific membrane) determine the overall cellular biophysical properties [1] and have been correlated with diseases such as malaria and cancer [2,3]
The microfluidic device consists of a constriction channel in polydimethylsiloxane (PDMS) elastomer that was replicated from a double-layer SU-8 mold
Based on the quantified aspiration length vs. time, the cellular entry process was divided into two stages
Summary
Mechanical properties of the cytoskeleton (Einstantaneous and Eequilibrium) and electrical properties of cell membrane (Cspecific membrane) determine the overall cellular biophysical properties [1] and have been correlated with diseases such as malaria and cancer [2,3]. Advances in microfluidic technologies have enabled mechanical and/or electrical property characterization of single cells in a continuous manner [8,9,10,11] (e.g., Einstantaneous values from hundreds of A549 cells [12] and Cspecific membrane values from hundreds of H1299 cells [13,14]). There are three types of devices developed to combine the measurements of cellular mechanical and electrical properties. These approaches were based on principles of microcantilever-based electrodes [15], micropipette aspiration with impedance spectroscopy [16], and constriction channel with impedance spectroscopy [17,18], respectively. Approaches using microcantilever-based electrodes [15] and the combination of micropipette aspiration with impedance spectroscopy [16] have limited throughput and cannot collect data from hundreds of single cells
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