Figure 2.

Cell penetration impedance detection with an empty (pressurized to 3000hPa) CNP. (A) Micrographs of probing the cell cytoplasm. i) The CNP is outside of the cell, (the nucleus outlined with a red line). ii) The CNP has just contacted the cell membarne. iii) The CNP lowered into the cell. (B) Probing the cell nucleus. i) The CNP is outside of the cell, (the nucleus outlined with a red line). ii) The CNP has just contacted the cell. iii) The CNP has been lowered into the nucleus. Membrane contact/penetration is indicated by the bright spot at the pipette’s tip due to the phase contrast filter, enhancing the contrast at the deformed membrane cleft. The CNP tip is identified with red arrows. Scale bar 10µm. (C) Schematics showing the CNP’s tip positions: in the extracellular solution (EC, left), in the cell cytoplasm (C, middle), in the cell nucleus (N, right). (D) The measured capacitance as a function of time before, during, and after penetration into the cell cytoplasm and the nucleus. (E) The capacitance (Top) and the normalized capacitance time derivative (Bottom) as functions of time for cytoplasmic (C) and nuclear (N) probing events in different cells with the same CNP. (F) Re{Z} (Top) and its normalized time-derivative (Bottom) as functions of time for the same probing events in panel C. The dashed lines in (E) and (F) represent possible threshold values for identifying cytoplasmic and nuclear penetration.