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Impedance measurement of cells using electric cell-substrate impedance sensing (ECIS) is widely accepted as an effective method to assess cell status. However, the sensitive frequency drifts over time with the changes of culture condition according to the built circuit model and experimental results. The area-normalized impedance spectrum (ANIS) method, which uses normalized area of impedance spectrum in a certain interval to assess cell viability, was proposed in this paper to solve the problem. The certain interval is calculated due to the threshold Zth, which is determined by 2% decline of the maximum impedance. Stabilities of two methods were analyzed by normalizing the area and impedance, showing that the normalized impedance fluctuated like a wave, while the normalized area was smoother. In addition, Cell Count Kit-8 (CCK-8) assay was carried out proving that the correlation index of ANIS method increases by 2.4% compared with impedance sensing method, and the maximum error of ANIS method decreases by 4%. Comparison analysis of two methods with random measurement noise was also discussed in this paper, and the results showed that the ANIS method was less affected by measurement noise than impedance sensing method. It demonstrated that the ANIS method is a more stable and accurate method to assess cell viability.

Activation of invasion and metastasis is recognized as one of the hallmarks of cancer. There are 90% of cancer-related deaths due to metastasis and given that it is worthy of note to study cancer progression and metastasis. Owing to restricted tools used to underpin the study of tumor invasion process, an on-site platform was developed to monitor this event in vitro. We used interdigital gold electrodes to monitor the dynamic process of cancer cells invading into extracellular matrix in situ continuously. Influences of collagen concentration and number of cancer cells on the measured impedance was exhibited. In addition, the parameters used to demonstrate the experiment results were optimized. The change of impedance magnitude indicated the cell-matrix interaction during invasion process. The potential further use of this platform would be complementary in cell studies when concerning metastasis.

Interest in impedance-based cellular assays is rising due to their remarkable advantages, including label-free, low cost, non-invasive, non-destructive, quantitative and real-time monitoring. In order to test their potential in cancer treatment decision and early detection of chemoresistance, we devised a new custom-made impedance measuring system based on electric cell-substrate impedance sensing (ECIS), optimized for long term impedance measurements. This device was employed in a proof of concept cell culture impedance analysis for the characterization of chemo-resistant colon cancer cells. Doxorubicin-resistant HT-29 cells were used for this purpose and monitored for 140 h. Analysis of impedance-based curves reveal different trends from chemo-sensitive and chemo-resistant cells. An impedance-based cytoxicity assay with different concentrations of doxorubicin was also performed using ECIS. The obtained results confirm the feasibility of ECIS in the study of drug resistance and show promises for studies of time-dependent factors related to physiological and behavioral changes in cells during resistance acquisition. The methodology presented herein, allows the continuous monitoring of cells under normal culture conditions as well as upon drug exposure. The ECIS device used, sets the basis for high-throughput early detection of resistance to drugs, administered in the clinical practice to cancer patients, and for the screening of new drugs in vitro, on patient-derived cells.

Portable low-cost sensors and sensing systems for the identification and quantitative measurement of bacteria in field water are critical in preventing drinking water from being contaminated by bacteria. In this article, we reported the design, fabrication and testing of a low-cost, miniaturized and sensitive bacteria sensor based on electrical impedance spectroscopy method using a smartphone as the platform. Our design of microfluidics enabled the pre-concentration of the bacteria which lowered the detection limit to 10 bacterial cells per milliliter. We envision that our demonstrated smartphone-based sensing system will realize highly-sensitive and rapid in-field quantification of multiple species of bacteria and pathogens.

The present work reports the impedimetric characterization of cellular activities of T47D cells treated with anticancer drug ZD6474 using impedance sensing devices. Four types of devices with different dimensions are fabricated by micromachining technology. Real time impedance monitoring data reveals spreading stage completes within 5 h. The frequency response characteristics of drug treated cells are studied to evaluate cytotoxic effect of ZD6474 along with the sensitivity variation for different designs. Compared to control data, a significant decrease in impedance data is observed for drug treated samples above 10 μM dose due to predominant cell death and detachment from the electrode surfaces. The quantitative relation developed between cell impedance and drug dose indicates that the magnitude of cell impedance varies inversely with the drug dose.

With the increasing need for multi-analyte point-of-care diagnosis devices, cell impedance measurement is a promising technique for integration with other sensing modalities. In this comprehensive review, the theory underlying cell impedance sensing, including the history, complementary metal–oxide–semiconductor (CMOS) based implementations, and applications are critically assessed. Whole cell impedance sensing, also known as electric cell-substrate impedance sensing (ECIS) or electrical impedance spectroscopy (EIS), is an approach for studying and diagnosing living cells in in-vitro and in-vivo environments. The technique is popular since it is label-free, non-invasive, and low cost when compared to standard biochemical assays. CMOS cell impedance measurement systems have been focused on expanding their applications to numerous aspects of biological, environmental, and food safety applications. This paper presents and evaluates circuit topologies for whole cell impedance measurement. The presented review compares several existing CMOS designs, including the classification, measurement speed, and sensitivity of varying topologies.

A microfluidic sensor for detection of cells flowing in a microchannel is presented. The sensor consists of a PDMS (PolyDiMethylSiloxane) layer with two planar microreservoirs connected by a microchannel. The bottom sides of the microreservoirs are faced to two sensing electrodes realized on a PCB (Printed Circuit Board). A noncontact measurement is ensured by an insulator layer between the electrodes and the fluid. Particles flowing in the microchannel cause changes in the conductivity of the narrow path formed by the fluid, producing variations in the impedance between the electrodes. A tailored electronic interface based on a DDS (Direct Digital Synthesis) device is proposed to measure the impedance variations. In the experimental tests, the cell flow is detected by changes in the effective capacitance and conductance between electrodes. These preliminary results are promising for biological measurements such as counting and sizing of cells in different matrices.

Bacteriophages are viruses that recognize specific receptors on the bacterium surface to which they bind and inject genetic material. The specificity of this recognition opens remarkable possibilities for biosensor development. The chemical attachment of T4 bacteriophages onto gold surfaces is being reported. This attachment leverages the genetic biotinylation of the capsid heads of bacteriophages, and the natural affinity of the biotin/streptavidin system. The development of a streptavidin-immobilization chemistry that minimizes non-specific binding of the target bacterium is first described. The attachment of genetically biotinylated T4 bacteriophages onto these streptavidin-coated surfaces is then reported. Such chemical immobilization results in a 15-fold improvement of attachment when compared to the simple physisorption of the wild-type phage onto bare gold. The attachment procedure was then used to investigate the effect of a biotinylated phage-terminated surface on the growth of the host bacteria. This assessment was conducted in an electric cell-substrate impedance sensing device. The streptavidin-mediated attachment of biotinylated phages significantly delays the growth of the host bacteria by up to 17.2 h. In comparison, non-specific binding of wild-type phages onto the streptavidin surface is found to cause a lesser growth delay of 13 h.

Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress that may be regulated by growth factor such as Endothelin-1 (ET-1). The majority of existing techniques to monitor hypertrophy in vitro are based on florescence probes designed to show morphological and biochemical alterations indicative of cardiomyocyte hypertrophy. In this work, a new cardiomyocyte-based impedance sensing system with the assistance of dielectrophoresis (DEP) cell concentration is developed to monitor the dynamics process of ET-1 induced cardiomyocyte hypertrophy. This device can increase the sensitivity of the impedance system and also has the potential to reduce the time for detection by a significant factor.

Transepithelial resistance (TER) measurement has often been used to study the paracellular transport properties of epithelia grown on permeable filters, especially the barrier function of tight junctions. However, the TER value includes another source, the resistance caused by cell–substrate contact, that may give rise to a high TER value if cell–substrate separation is small. In this study we use electric cell–substrate impedance sensing (ECIS) to measure both paracellular resistance and the average cell–substrate distance of MDCK (II), HEp-2, and WI-38 VA13 cells. Comparing ECIS data with those from TER measurements of cell layers cultured on polycarbonate filters, we can obtain the approximate extra resistance resulting from cell–substrate contact for each cell type. The value of cell–substrate resistance was also estimated by two theoretical calculations that bracket the true values. Our results demonstrate that cell–substrate contact substantially influences the TER data measured using polycarbonate filters and that the extra resistance due to cell–substrate spaces depends on both cell type and filter property.