Biophysical phenotyping of cells via impedance spectroscopy in parallel cyclic deformability channels

Abstract

This paper describes a new microfluidic biosensor with capabilities of studying single cell biophysical properties. The chip contains four parallel sensing channels, where each channel includes two constriction regions separated by a relaxation region. All channels share a pair of electrodes to record the electrical impedance. Single cell impedance magnitudes and phases at different frequencies were obtained. The deformation and transition time information of cells passing through two sequential constriction regions were gained from the time points on impedance magnitude variations. Constriction channels separated by relaxation regions have been proven to improve the sensitivity of distinguishing single cells. The relaxation region between two sequential constriction channels provides extra time stamps that can be identified in the impedance plots. The new chip allows simultaneous measurement of the biophysical attributes of multiple cells in different channels, thereby increasing the overall throughput of the chip. Using the biomechanical parameters represented by the time stamps in the impedance results, breast cancer cells (MDA-MB-231) and the normal epithelial cells (MCF-10A) could be distinguished by 85%. The prediction accuracy at the single-cell level reached 97% when both biomechanical and bioelectrical parameters were utilized. While the new label-free assay has been tested to distinguish between normal and cancer cells, its application can be extended to include cell-drug interactions and circulating tumor cell detection in blood.

Positional dependence of particles and cells in microfluidic electrical impedance flow cytometry: origin, challenges and opportunities

“…Even if a narrow channel would obviate the need for focusing, a smaller channel section would increase the risk of clogging as well as the pressure drop. Although microfluidic devices with constriction channels have been developed 85,86 , their ability to handle a large range of different sized particles remains limited compared to classical microfluidic devices. To cope with the positional dependence without the associated risk of clogging the channel, other methods have been developed.…”

Recent Advances in Electrical Impedance Sensing Technology for Single-Cell Analysis

“…Recent IFC devices applied in single-cell analysis are summarized in Table 1 . These applications, discussed in this subsection, are simply classified according to cell species, including blood cells [ 110 , 111 , 112 , 113 , 114 ], tumor cells [ 43 , 52 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ], stem cells [ 123 , 124 , 125 , 126 , 127 ], plant cells [ 60 , 128 , 129 , 130 , 131 , 132 ] and microbes [ 53 , 62 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ]. In terms of blood cells, researchers focused on the identification and counting of normal or diseased blood cells.…”

“…In terms of blood cells, researchers focused on the identification and counting of normal or diseased blood cells. Studies showed the capability of IFC devices in recognition of different types of dissociated tumor cells (DTCs) [ 43 , 118 , 120 , 121 ] or circulating tumor cells (CTCs) [ 52 , 115 , 119 , 122 ]. As for stem cells, the main focus is the impedance measurement of their long-term differentiation process.…”

“…Choi et al proposed a simple DC impedance microcytometer for identifying CTCs according to the cell volume [ 115 ]. Ren et al reported an IFC device featuring parallel cyclic deformability channels and coplanar electrodes, to collect both biomechanical and bioelectrical properties for tumor cell analysis [ 119 ]. The deformation and transition time of tumor cells could be obtained from the time points when impedance amplitude changes abruptly ( Figure 5 B).…”

“…( B ) Recording of the impedance variation when a breast cancer cell (MDA-MB-231) passing through the constriction channel. Reproduced from [ 119 ] with the permission from American Institute of Physics. ( C ) Scatter plot of opacity (|Z 2MHz |/|Z 500kHz |) and electric diameter (|Z 500kHz | 1/3 ) for MCF-7 cells and other blood cells.…”