A frequency-dependent cell impedance analysis chip for applications to cancer cell and normal cell discrimination

Abstract

This thesis presents a frequency-dependent cell impedance analysis chip for use in cancer and normal cell discrimination. The previous cell impedance analysis chips for flowing cells do not allow enough time for cell-to-electrode contact to monitor frequency-dependent impedance response. Another type of the previous cell impedance analysis chips for the cells clamped by membranes need complex sample control for making stable cell-to-electrode contact. We present a new impedance analysis chip using the SU8 microchamber array, on which a PDMS cover is placed to make stable cell-to-electrode contact for the individual cell trapped in each microchamber; thus achieving frequency-dependent single-cell impedance analysis without complex sample control.We design and fabricate the array of 24 microchambers, each having size of 32x32x12 μm3, so that the PDMS cover traps individual cells in the microchambers to make the cell-to-electrode contact diameter as 80% of 20μm-diameter cells. Using the fabricated chip, we have measured and compared the impedance (magnitude and phase) response of human lung cancer cells (H358, A549) with the response of normal lung cells (the human brachial/tracheal epithelial cells of NHBE) in the frequency range of 200Hz to 2MHz for the AC signal of 100mVp-p. Compared to the normal cells, the cancer cells show impedance response difference: the magnitude difference of 28.30kΩ~151.67kΩ in the frequency range of 95.6 kHz~2MHz and the phase difference of 1.97°~16.83° in frequency range of 4.37 kHz~2MHz, respectively. In particular, the normal cells shows significant phase difference of 14.24°~16.83° comparing to the both cancer cells in the frequency range of 15.0 kHz~27.8 kHz. It is demonstrated experimentally that the impedance analysis chip performs frequency-dependent cell impedance analysis by making stable cell-to-electrode contact with simple sample control; thereby applicable to the normal cell and cancer cell discrimination for furthe...