Microelectrical Impedance Spectroscopy Research Articles

Integration of tri-polar microelectrodes for performance enhancement of an impedance biosensor

This paper demonstrates the effect of microelectrodes configuration on the sensitivity and accuracy of the micro-electrical impedance spectroscopy (μEIS). Bi-polar and tri-polar microelectrodes configurations were presented, fabricated and experimentally used to extract the electrical parameters of Human Bone Osteosarcoma Epithelial (U2OS) viable and dead cells. A comparison between the experimental results are presented and discussed. These experimental results show that the tri-polar electrode configuration has higher sensitivity compared to bi-polar configuration.

Editorial Desai et al. as Part of the Special Section on IEEE EMBS Conference on Micro and Nanotechnology in Medicine

Due to an oversight, we failed to include the paper by Salil P. Desai et al entitled “Micro-Electrical Impedance Spectroscopy and Identification of Patient-Derived, Dissociated Tumor Cells” [Item 1) of the Appendix] in the Special Section devoted to the 2018 IEEE EMBS Conference on Micro and Nanotechnology in Medicine in a recent issue of the IEEE Transactions on NanoBioscience [Item 2) of the Appendix].

Micro-Electrical Impedance Spectroscopy and Identification of Patient-Derived, Dissociated Tumor Cells.

Fine needle aspirate sampling of tumors requires acquisition of sufficient cells to complete a diagnosis. Aspirates through such fine needles are typically composed of small cell clusters in suspension, making them readily amenable to microfluidic analysis. Here we show a microfluidic device with integrated electrodes capable of interrogating and identifying cellular components in a patient-derived sample of dissociated tumor cells using micro-electrical impedance spectroscopy ( μ EIS). We show that the μ EIS system can distinguish dissociated tumor cells in a sample consisting of red blood cell (RBCs) and peripheral blood mononucleated cells (PBMCs). Our μ EIS system can also distinguish dissociated tumor cells from normal cells and we show results for five major cancer types, specifically, lung, thyroid, breast, ovarian, and kidney cancer. Moreover, our μ EIS system can make these distinctions in a label-free manner, thereby opening the possibility of integration into standard clinical workflows at the point of care.

Electrophysiological differences between typical and dense benign prostatic hyperplasia tissues retrieved after holmium laser enucleation of the prostate

Electrophysiological differences between typical and dense (beach ball) benign prostatic hyperplasia (BPH) tissues were investigated using a needle device with a micro-electrical impedance spectroscopy (µEIS) sensor. Ten pieces of typical BPH tissues and beach balls were collected from ten patients during the morcellation procedure of Holmium laser enucleation of the prostate. Their impedance was measured at a frequency range from 100 to 1 MHz using the µEIS-on-a-needle (µEoN). The impedance data (magnitude) were compared between the two tissue types and their correlation with the pathologic features was investigated. The mean magnitude of the beach balls tended to be larger than that of the typical BPH tissues at all investigated frequencies. Notably, significantly larger magnitudes were observed in the beach balls at the frequencies higher than 15.9 kHz (p ≤ 0.02). The variation of mean log-transformed magnitudes by frequency was significantly different between both tissue types (p < 0.001). The pathologic features of the beach balls presented pure stromal nodules of nodular hyperplasia, while the typical BPH tissues presented mixed epithelial-stromal nodules. The impedance difference between typical BPH tissues and beach balls is assumed to be attributed to the amount of their stromal content.

Differentiation Between Normal and Cancerous Human Urothelial Cell Lines Using Micro-Electrical Impedance Spectroscopy at Multiple Frequencies

The present study aims to investigate differences in impedance between normal (SV-HUC-1) and cancerous (TCCSUP) human urothelial cell lines at multiple frequencies by using a micro-electrical impedance spectroscopy (µEIS) device. A µEIS device was designed to measure the impedance of SV-HUC-1 and TCCSUP cells as the cells passed the sensing electrodes in the microfluidic channel. The cellular impedance was measured at frequencies of 10, 50, 100, 500 kHz, and 1 MHz, and the impedance values were compared at each frequency to investigate differences between the two cell lines. Additionally, the linear correlation between impedance and frequency was analyzed. The number of SV-HUC-1 and TCCSUP cells measured was 13 and 9, 21 and 10, 16 and 24, 8 and 8, and 11 and 22 cells at the frequencies of 10, 50, 100, 500 kHz, and 1 MHz, respectively. TCCSUP had significantly smaller amplitudes than SV-HUC-1 at 10, 50, and 100 kHz (p = 0.030, p = 0.031, and p < 0.001, respectively). Moreover, significant differences in phase angle were observed between cell lines at 100, 500 kHz, and 1 MHz (p < 0.001 in all). A significant difference between cell lines in terms of amplitude and phase angle was observed concurrently at 100 kHz. The amplitude of both the cell lines was negatively correlated to frequency, while the phase angle presented no correlation. In conclusion, the µEIS device could effectively differentiate between SV-HUC-1 and TCCSUP on the basis of their impedance.

Microelectrical Impedance Spectroscopy for the Differentiation between Normal and Cancerous Human Urothelial Cell Lines: Real-Time Electrical Impedance Measurement at an Optimal Frequency.

Purpose. To distinguish between normal (SV-HUC-1) and cancerous (TCCSUP) human urothelial cell lines using microelectrical impedance spectroscopy (μEIS). Materials and Methods. Two types of μEIS devices were designed and used in combination to measure the impedance of SV-HUC-1 and TCCSUP cells flowing through the channels of the devices. The first device (μEIS-OF) was designed to determine the optimal frequency at which the impedance of two cell lines is most distinguishable. The μEIS-OF trapped the flowing cells and measured their impedance at a frequency ranging from 5 kHz to 1 MHz. The second device (μEIS-RT) was designed for real-time impedance measurement of the cells at the optimal frequency. The impedance was measured instantaneously as the cells passed the sensing electrodes of μEIS-RT. Results. The optimal frequency, which maximized the average difference of the amplitude and phase angle between the two cell lines (p < 0.001), was determined to be 119 kHz. The real-time impedance of the cell lines was measured at 119 kHz; the two cell lines differed significantly in terms of amplitude and phase angle (p < 0.001). Conclusion. The μEIS-RT can discriminate SV-HUC-1 and TCCSUP cells by measuring the impedance at the optimal frequency determined by the μEIS-OF.

Quantification of the Heterogeneity in Breast Cancer Cell Lines Using Whole-Cell Impedance Spectroscopy

Quantification of the heterogeneity of tumor cell populations is of interest for many diagnostic and therapeutic applications, including determining the cancerous stage of tumors. We attempted to differentiate human breast cancer cell lines from different pathologic stages and compare that with a normal human breast tissue cell line by characterizing the impedance properties of each cell line. A microelectrical impedance spectroscopy system has been developed that can trap a single cell into an analysis cavity and measure the electrical impedance of the captured cell over a frequency range from 100 Hz to 3.0 MHz. Normal human breast tissue cell line MCF-10A, early-stage breast cancer cell line MCF-7, invasive human breast cancer cell line MDA-MB-231, and metastasized human breast cancer cell line MDA-MB-435 were used. The whole-cell impedance signatures show a clear difference between each cell line in both magnitude and phase of the electrical impedance. The membrane capacitance calculated from the impedance data was 1.94 +/- 0.14, 1.86 +/- 0.11, 1.63 +/- 0.17, and 1.57 +/- 0.12 muF/cm(2) at 100 kHz for MCF-10A, MCF-7, MDA-MB-231, and MDA-MB-435, respectively. The calculated resistance for each cancer cell line at 100 kHz was 24.8 +/- 1.05, 24.8 +/- 0.93, 24.9 +/- 1.12, and 26.2 +/- 1.07 MOhm, respectively. The decrease in capacitances of the cancer cell lines compared with that of the normal cell line MCF-10A was 4.1%, 16.0%, and 19.1%, respectively, at 100 kHz. These findings suggest that microelectrical impedance spectroscopy might find application as a method for quantifying progression of cancer cells without the need for tagging or modifying the sampled cells.

Microsystems for isolation and electrophysiological analysis of breast cancer cells from blood

This paper presents the development of a microsystem for separating suspended breast cancer cells in peripheral blood and for sorting them based on their electrophysiological characteristics. A continuous paramagnetic capture mode (PMC) magnetophoretic microseparator was utilized for the isolation of suspended breast cancer cells in peripheral blood based on the native magnetic properties of blood cells without any tagging such as with magnetic probes. A micro-electrical impedance spectroscopy (mu-EIS) system was used as a downstream cell analysis tool to extract the pathological characteristics from the breast cancer cells. The system was fabricated on silicon and glass substrates utilizing microfabrication and stereolithography technologies. The experimental results of the PMC microseparator show that 94.8% of the breast cancer cells could be continuously separated out from a spiked blood sample with a 0.2 T external magnetic flux. The electrical impedances of human breast cancer cell lines of different pathological stages (MCF-7, MDA-MB-231, and MDA-MB-435) were measured using mu-EIS and compared to those of normal human breast tissue cell line MCF-10A.

Particle detection by electrical impedance spectroscopy with asymmetric-polarization AC electroosmotic trapping

Recently, considerable interest and effort have been devoted to the on-site detection of low-concentration pathogenic bacteria in order to deter infectious diseases and bioterrorism. Conventionally, bacteria detection involves culturing, which is time-consuming and unfeasible under field conditions. Microfluidic devices with integrated electrical detection will enable fast, low-cost, and portable sensing and processing of biological and chemical samples. AC electroosmosis (EO) is well-suited for integration into microsystems due to its low-voltage operation and no-moving-part implementation and microelectrical impedance spectroscopy can be integrated with AC EO for particle manipulation, leading to enhanced sensitivity due to a reduction of the transport time to the detector. Experiments are performed to find optimal conditions for obtaining particle and bacterial assembly lines on electrodes by AC EO and preliminary results show good resolution at a concentration of 104 bacteria/ml, indicating that combining AC EO with impedance measurement can improve the sensitivity of particle electrical detection.