Xiaotian Du

Broadband single-cell detection with a coplanar series gap

Using a coplanar waveguide with a series gap in conjunction with dielectrophoresis trapping, consecutive S-parameter measurements between 0.5 and 20 GHz were quickly performed with and without a Jurkat cell trapped to compensate for a relatively noisy and drifting background. This allowed the small cytoplasm capacitance, on the order of 10 fF, to be reliably extracted. The extracted cytoplasm capacitance is within a factor of 2 of the previously reported value by using a shunt trap but is believed to be more accurate. The present technique can complement previously developed microwave and RF techniques in characterizing the capacitances and resistances of plasma and membrane for complete characterization of the electrical properties of a simple cell.

Reproducible broadband measurement for cytoplasm capacitance of a biological cell

Using a coplanar waveguide with a series gap in conjunction with dielectrophoresis trapping, consecutive S-parameter measurements between 0.5 and 20 GHz were quickly performed with and without a Jurkat cell trapped to compensate for a relatively noisy and drifting background. Based on sixteen measurements repeated on eight live cells and eight dead cells, differences in both return and insertion losses show two distinct distributions indicating either return loss or insertion loss alone can be used to distinguish a live cell from a dead one. Further, since the frequency dependence is generally linear or absent, discrete-frequency measurement (as opposed to sweep-frequency measurement) of return or insertion loss may suffice. If proven statistically by a much larger number of cells, this should greatly speed up the measurement to facilitate its eventual field use.

High-frequency continuous-wave electroporation of Jurkat human lymphoma cells

Electroporation of Jurkat human lymphoma cells were investigated under 10-MHz continuous waves and benchmarked against that at 100 kHz. Both cell poration and cell death were monitored in real time by fluorescence microscopy and found to occur at approximately three times higher voltages at 10 MHz than that at 100 kHz. This difference in voltage could not be completely accounted for by order-of-magnitude estimate of cytoplasm resistance and membrane capacitance. Better modeling and simulation of the cell structure and property are required to accurately predict the frequency dependence of electroporation.

Distributed Effect in High-Frequency Electroporation of Biological Cells

Electroporation of Jurkat T-lymphoma human cells was investigated using 10-MHz continuous waves and benchmarked against that at 100 kHz. Both cell poration and cell death were simultaneously monitored by fluorescence microscopy, and found to occur under approximately four times higher voltages at 10 MHz than that at 100 kHz. This weaker-than-expected increase in poration threshold could be explained by detailed analysis of the distributed effect often ignored in electroporation studies.

Correlation between morphology change and microwave property during single-cell electroporation

Traditionally, electroporation of biological cells is tracked by fluorescence microscopy with chemical dyes that tend to be slow and invasive. This paper reports, for the first time, electroporation tracked by real-time change in the microwave insertion loss, which is correlated with simultaneous change in cell morphology recorded through an optical microscope. The change in insertion loss was found to be faster and more abrupt than the change in cell morphology, although the latter was still faster than fluorescence microscopy. Although more work is needed to verify whether these changes correspond to a reversible electroporation or not, the present result suggests that real-time microwave characterization can be a faster and less invasive technique for early detection of electroporation. Additionally, although the electroporation is presently performed on Jurkat human lymphoma cells, it is believed that the same technique can be extended to many other types of cells.

Ultra-wideband electromagnetic detection of biological cells

Traditionally, electromagnetic detection of biological cells was conducted at either radio or microwave frequencies, which was sensitive to either cellular or subcellular properties, respectively. This paper reports for the first time a single sweep from megahertz to gigahertz frequencies so that cell viability, membrane capacitance, cytoplasm resistance, and cytoplasm capacitance could be determined simultaneously. These parameters were determined with the aid of simple cell model and equivalent circuit, despite great challenges in ultra-wideband measurement and analysis. Although the extracted parameter values for Jurkat T-lymphocytes human cells, live or dead, were consistent with that reported in the literature, more careful measurement and analysis are required in the future, especially for electromagnetic detection over an even wider bandwidth. In any case, the present analysis confirmed that it was easier to assess cell viability around 100 MHz but cytoplasm characteristics around 10 GHz.

Preliminary results for broadband electrical detection of live bacteria

For the first time, broadband (0.5-20 GHz) electrical detection of live bacteria was successfully demonstrated on E. coli, despite their being small and adherent compared to mammalian cells such as Jurkat T-lymphoma human cells that had been detected by using a similar coplanar waveguide in conjunction with a microfluidic channel. Critical to the success was in suppressing the background drift of the insertion and return losses to the order of 0.01 dB. Presently, it is estimated that approximately 104 E. coli were required to yield a statistically significant signal in the insertion/return losses. Therefore, to detect a single bacterium, the measurement sensitivity and the background stability need to be further improved by orders of magnitude in the future.