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Impedance assessment in living biological cells has gained popularity as a label-free, real-time, and quantitative analytical approach for determining cellular states. Electric cell substrate impedance sensing (ECIS) provides valuable insights into cell adhesion, the intricate interactions between cells and their underlying substrate, and cellular communication. Further, the ECIS method's high sensitivity enables the observation of biological events at the single-cell level and the precise determination of cell-substrate distances at the nanoscale. Importantly, using cellular electrical properties as a valuable marker, ECIS can shed light on how cancer cells proliferate, migrate, and invade. In this article, we discuss electric cell-substrate impedance sensing as it relates to electrode design, manufacturing, and application in impedance measurement. The present review also outlines our current understanding of the advantages of ECIS in studying cancer cell behavior and drug screening and their prospective future modifications. Impedance-sensing approaches in biology have many potential applications, including point-of-need diagnostics, highly specialized devices, and seamless integration. In summary, this impedance-based technology might one day be an attractive diagnostic tool in cancer research.

Purpose: During traditional insertion of cochlear implant (CI) electrode arrays (EAs), surgeons rely on limited tactile feedback and visualization of the EA entering the cochlea to control the insertion. One insertion approach for precurved EAs involves slightly overinserting the EA and then retracting it slightly to achieve closer hugging of the modiolus. In this work, we investigate whether electrical impedance sensing could be a valuable real-time feedback tool to advise this pullback technique. Methods: Using a to-scale 3D-printed scala tympani model, a robotic insertion tool, and a custom impedance sensing system, we performed experiments to assess the bipolar insertion impedance profiles for a cochlear CI532/632 precurved EA. Four pairs of contacts from the 22 electrode contacts were chosen based on preliminary testing and monitored in real time to halt the robotic insertion once the closest modiolar position had been achieved but prior to when the angular insertion depth (AID) would be reduced. Results: In this setting, the open-loop robotic insertion impedance profiles were very consistent between trials. The exit of each contact from the external stylet of this EA was clearly discernible on the impedance profile. In closed-loop experiments using the pullback technique, the average distance from the electrode contacts to the modiolus was reduced without greatly affecting the AID by using impedance feedback in real time to determine when to stop EA retraction. Conclusion: Impedance sensing, and specifically the access resistance component of impedance, could be a valuable real-time feedback tool in the operating room during CI EA insertion. Future work should more thoroughly analyze the effects of more realistic operating room conditions and inter-patient variability on this technique. [ABSTRACT FROM AUTHOR]

The electrical properties of many biological tissues are freely available from the INRC and the IT'IS databases. However, particularly in lower frequency ranges, few studies have investigated the optimal measurement protocol or the key confounders that need to be controlled, monitored, and reported. However, preliminary work suggests that the contact force of the measurement probe on the tissue sample can affect the measurements. The aim of this paper is to investigate the conductivity change due to the probe contact force in detail. Twenty ex vivo bovine heart samples are used, and conductivity measurements are taken in the Left Atrial Appendage, a common target for medical device developments. The conductivity measurements reported in this work (between 0.14 S/m and 0.24 S/m) align with the literature. The average conductivity is observed to change by −21% as the contact force increases from 2 N to 10 N. In contrast, in conditions where the fluid concentration in the measurement area is expected to be lower, very small changes are observed (less than 2.5%). These results suggest that the LAA conductivity is affected by the contact force due to the fluid concentration in the tissue. This work suggests that contact force should be controlled for in all future experiments. [ABSTRACT FROM AUTHOR]

The electrical properties of many biological tissues are freely available from the INRC and the IT’IS databases. However, particularly in lower frequency ranges, few studies have investigated the optimal measurement protocol or the key confounders that need to be controlled, monitored, and reported. However, preliminary work suggests that the contact force of the measurement probe on the tissue sample can affect the measurements. The aim of this paper is to investigate the conductivity change due to the probe contact force in detail. Twenty ex vivo bovine heart samples are used, and conductivity measurements are taken in the Left Atrial Appendage, a common target for medical device developments. The conductivity measurements reported in this work (between 0.14 S/m and 0.24 S/m) align with the literature. The average conductivity is observed to change by −21% as the contact force increases from 2 N to 10 N. In contrast, in conditions where the fluid concentration in the measurement area is expected to be lower, very small changes are observed (less than 2.5%). These results suggest that the LAA conductivity is affected by the contact force due to the fluid concentration in the tissue. This work suggests that contact force should be controlled for in all future experiments.

This article presents a fully integrated multi-modal CMOS cellular sensor/stimulator array chip with 21 952 pixels and 1568-pixel concurrent readouts, while each array pixel can be independently reconfigured to support three sensing and one stimulation modalities: cellular potential recording, optical-point impedance sensing, and bi-phasic current stimulation. The CMOS sensor/stimulator array chip provides 3.6 mm $\times $ 1.6 mm active field-of-view (FoV). Each pixel contains one 8 $\mu \text{m}\,\,\times $ 8 $\mu \text{m}$ gold deposited electrode, one 6 $\mu \text{m}\,\,\times $ 6 $\mu \text{m}$ photodiode, and in-pixel circuits within 8 $\mu \text{m}\,\,\times $ 11 $\mu \text{m}$ pixel area, while the pixel-to-pixel pitch is 16 $\mu \text{m}\,\,\times $ 16 $\mu \text{m}$. As a proof of concept, the CMOS array is implemented in a standard 130-nm BiCMOS process. Comprehensive electrical testing (potential/optical/four-point impedance/stimulation) and biological measurements (potential/optical/four-point impedance) with on-chip rat cardiomyocytes demonstrate the functionalities and unique advantages of this multi-modality cellular array. With high throughput multi-modal cellular sensing supported at the pixel level, this array chip enables holistic characterization of on-chip cellular samples with single-cell resolution. [ABSTRACT FROM AUTHOR]

The organic electrochemical transistor (OECT) has attracted interest for use in biosensor technology due to its ability to transduce ionic to electronic signals and operate in aqueous environments. While OECTs have been broadly applied for biosensing and impedance characterization of biological systems, there is still no consensus on the ideal geometries, relative capacitances, and operational conditions for specific sensing scenarios. Here it is shown that for impedance sensing with a capacitive layer on the gate, gate‐limited OECTs produce the largest sensor response. An equivalent circuit model is used to study frequency response with non‐permeable and ion‐permeable membranes added to the gate and found that the transistor configuration, with respect to gate and channel capacitances, able to produce the largest sensor signal is determined by the capacitance to be sensed as well as the membrane permeability. The findings are applied to design a gold gate OECT capable of detecting formation of a lipid bilayer on the gate. The results indicate that high transconductance OECTs typically considered attractive do not deliver the largest sensor signals when used for impedance sensing. Results are presented in settings similar to those used in practical experiments, thereby providing guidance on how to best design OECTs for impedance biosensing. [ABSTRACT FROM AUTHOR]

Background: Cochlear-implant electrode arrays (EAs) are currently inserted with limited feedback, and impedance sensing has recently shown promise for EA localisation., Methods: We investigate the use of impedance sensing to infer the progression of an EA during insertion., Results: We show that the access resistance component of bipolar impedance sensing can detect when a straight EA reaches key anatomical locations in a plastic cochlea and when each electrode contact enters/exits the cochlea. We also demonstrate that dual-sided electrode contacts can provide useful proximity information and show the real-time relationship between impedance and wall proximity in a cadaveric cochlea for the first time., Conclusion: The access resistance component of bipolar impedance sensing has high potential for estimating positioning information of EAs relative to anatomy during insertion. Main limitations of this work include using saline as a surrogate for human perilymph in ex vivo models and using only one type of EA., (© 2024 John Wiley & Sons Ltd.)

Electric Cell-Substrate Impedance Sensing (ECIS), xCELLigence and cellZscope are commercially available instruments that measure the impedance of cellular monolayers. Despite widespread use of these systems individually, direct comparisons between these platforms have not been published. To compare these instruments, the responses of human brain endothelial monolayers to TNFα and IL1β were measured on all three platforms simultaneously. All instruments detected transient changes in impedance in response to the cytokines, although the response magnitude varied, with ECIS being the most sensitive. ECIS and cellZscope were also able to attribute responses to particular endothelial barrier components by modelling the multifrequency impedance data acquired by these instruments; in contrast the limited frequency xCELLigence data cannot be modelled. Consistent with its superior impedance sensing, ECIS exhibited a greater capacity than cellZscope to distinguish between subtle changes in modelled endothelial monolayer properties. The reduced resolving ability of the cellZscope platform may be due to its electrode configuration, which is necessary to allow access to the basolateral compartment, an important advantage of this instrument. Collectively, this work demonstrates that instruments must be carefully selected to ensure they are appropriate for the experimental questions being asked when assessing endothelial barrier properties.

Highlights • Tin disulfide/graphene oxide nanoflower (SnS 2 /GO) was firstly prepared on a flexible PET substrate. • The SnS 2 /GO film sensor shows ultrasensitive humidity sensing with ultralow hysteresis and good reversibility. • The SnS 2 /GO film humidity sensor demonstrated a great potential for wearable applications. Abstract Flexible humidity sensors with ultrafast response are great importance in the promising wearable devices. In this paper, a novel nanocomposite of tin disulfide/graphene oxide nanoflower (SnS 2 /GO) was first synthesized for constructing humidity sensors. The nanostructural, morphological and compositional properties of the SnS 2 /GO hybrid were characterized by XRD, XPS, FT-IR, SEM, TEM and EDS. The humidity experiment found that SnS 2 /GO (in the wt% ratio of 1:2.5) has the most excellent response. The humidity sensing results revealed the SnS 2 /GO film sensor has ultrahigh response, negligible hysteresis, favorable reversibility and ultrafast response/recovery behavior, which outstrips the individual SnS 2 or GO film sensor. The potential mechanism of water molecule adsorption was revealed, and the complex impedance spectroscopy and Bode diagrams were used to further explain the sensing mechanisms of the SnS 2 /GO composite. Moreover, the impedance changes caused by the bending effect, human respiration and fingertip approaching/retracting behavior were investigated, which demonstrate a great potential of the SnS 2 /GO sensor in humidity sensing for wearable applications. [ABSTRACT FROM AUTHOR]

Abstract Traditional methods for detection of metabolically-active bacterial cells, while effective, require several days to complete. Development of sensitive electrical biosensors is highly desirable for rapid detection and counting of pathogens in food, water, or clinical samples. Herein, we develop a highly-sensitive non-Faradaic impedance sensor which detects metabolic activity of E. coli cells in a mere 1 μl of sample volume and without any sample filtration/purification. The three dimensional (3D) interdigitated electrodes (IDEs) along with self-assembled gold-nickel (Au-Ni) nanostructures significantly amplify the sensitivity by increasing the sensing area almost three-fold. The developed microsystem is integrated with an agar-based growth medium and monitors the metabolism of bacterial cells, enabling bacterial detection in approximately one hour after inoculation, i.e. in the lag-phase. Incorporation of a secondary agar layer as a biocompatible passivation layer protects the IDEs from potential Faradaic reactions and enhances sensitivity to modulation of the non-Faradaic impedance due to cellular metabolism. The resultant label-free sensor is capable of selective identification of metabolizing cells (vs. dead cells) across a wide linear range (10–1000 cells/μl). These results help pave the way for rapid antibacterial susceptibility testing at the point-of-need, which is currently a major challenge in healthcare. Highlights • Non-Faradaic impedance sensor selectively detects metabolism of 10 cells/μl of E. co li K12 in just 1 h. • Metabolism is detected in lag-phase, as opposed to log-phase which takes significantly longer time. • 3D gold-nickel microelectrodes increase sensing area almost three-fold. • Sensor performance is improved by integration with a gel-based passivation layer. • Integration with gel-based culture medium enables in situ detection, with no sample preparation. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Chlorpromazine (CPZ) is a neuroleptic drug and prototype compound used to study intrahepatic cholestasis. The exact mechanisms of CPZ induced cholestasis remain unclear. Rat hepatocytes, or a sandwich culture of rat and human hepatocytes, have been the most commonly used models for studying CPZ toxicity in vitro. However, to better predict outcomes in pre-clinical trials where cholestasis may be an unwanted consequence, a human in vitro model, based on human HepaRG cells, capable of real-time, non-invasive and label free monitoring, alongside molecular investigations would be beneficial. To address this we used the human hepatic HepaRG cell line, and established concentrations of CPZ ranging from sub-toxic, 25 μM and 50 μM, to toxic 100 μM and compared them with untreated control. To assess the effect of this range of CPZ concentrations we employed electrical cell-substrate impedance sensing (ECIS) to measure viability and cell membrane interactions alongside traditional viability assays, immunocytostaining and qRT-PCR to assess genes of interest within adaptive and inflammatory pathways. Using these methods, we show a concentration dependant response to CPZ involving pro-inflammatory pathway, loss of tight junctions and membrane integrity, and an adaptive response mediated by Cytochrome P450 (CYP) enzyme activation and up-regulation of membrane phospholipid and xenobiotic transporters. In conclusion, structural changes within the membrane caused by sub-toxic and toxic concentrations of CPZ negatively impact the function of the cellular membrane. Damage to efflux transport proteins caused by CPZ induce cholestasis alongside downstream inflammation, which activates compensatory responses for cell survival. Lay summary Chlorpromazine is a drug used to treat patients with schizophrenia, which has a known association with liver damage. Here we show that it causes inflammation and alters the cell membranes in liver and bile duct cells similar to what is seen within a human population. The initiation of the inflammatory response and changes to cellular structure may provide insight into the damage and disease process and inform medical treatment. [ABSTRACT FROM AUTHOR]

Therapies based on regenerative techniques have the potential to radically improve healthcare in the coming years. As a result, there is an emerging need for non-destructive and label-free technologies to assess the quality of engineered tissues and cell-based products prior to their use in the clinic. In parallel, the emerging regenerative medicine industry that aims to produce stem cells and their progeny on a large scale will benefit from moving away from existing destructive biochemical assays towards datadriven automation and control at the industrial scale. Impedance-based cellular assays (IBCA) have emerged as an alternative approach to study stem-cell properties and cumulative studies, reviewed here, have shown their potential to monitor stem-cell renewal, differentiation and maturation. They offer a novel method to non-destructively assess and quality-control stem-cell cultures. In addition, when combined with in vitro disease models they provide complementary insights as label-free phenotypic assays. IBCA provide quantitative and very sensitive results that can easily be automated and up-scaled in multi-well format. When facing the emerging challenge of real-time monitoring of three-dimensional cell culture dielectric spectroscopy and electrical impedance tomography represent viable alternatives to two-dimensional impedance sensing. This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. [ABSTRACT FROM AUTHOR]

The detection of bacteria cells and their viability in food, water and clinical samples is critical to bioscience research and biomedical practice. In this work, we present a microfluidic device encapsulating a coplanar waveguide for differentiation of live and heat-killed Escherichia coli cells suspended in culture media using microwave signals over the frequency range of 0.5–20 GHz. From small populations of ∼15 E. coli cells, both the transmitted (| S 21 |) and reflected (| S 11 |) microwave signals show a difference between live and dead populations, with the difference especially significant for | S 21 | below 10 GHz. Analysis based on an equivalent circuit suggests that the difference is due to a reduction of the cytoplasm conductance and permittivity upon cell death. The electrical measurement is confirmed by off-chip biochemical analysis: the conductivity of cell lysate from heat-killed E. coli is 8.22% lower than that from viable cells. Furthermore, protein diffusivity increases in the cytoplasm of dead cells, suggesting the loss of cytoplasmic compactness. These changes are results of intact cell membrane of live cells acting as a semipermeable barrier, within which ion concentration and macromolecule species are tightly regulated. On the other hand, the cell membrane of dead cells is compromised, allowing ions and molecules to leak out of the cytoplasm. The loss of cytoplasmic content as well as membrane integrity is measurable by microwave impedance sensors. Since our approach allows detection of bacterial viability in the native growth environment, it is a promising strategy for rapid point-of-care diagnostics of microorganisms as well as sensing biological agents in bioterrorism and food safety threats. [ABSTRACT FROM AUTHOR]

Digestive health is critically dependent on the secretion of enzymes from the exocrine pancreas to the duodenum via the pancreatic duct. Specifically, pancreatic trypsin is a major protease responsible for breaking down proteins for absorption in the small intestine. Gelatin-based hydrogels, deposited in the form of thin films, have been studied as potential sensor substrates that hydrolyze in the presence of trypsin. In this work, we (1) investigate gelatin as a sensing material; (2) develop a fabrication strategy for coating sensor surfaces; and (3) implement a miniaturized impedance platform for measuring activity levels of pancreatic trypsin. Using impedance spectroscopy, we evaluate gelatin's specificity and rate of degradation when exposed to a combination of pancreatic enzymes in neutral solution representative of the macromolecular heterogeneity present in the duodenal environment. Our findings suggest gelatin's preferential degradation to trypsin compared to enzymes such as lipase and amylase. We further observe their interference with trypsin behavior in equivalent concentrations, reducing film digestion by as much as 83% and 77%, respectively. We achieve film patterns in thicknesses ranging from 300-700 nm, which we coat over interdigitated finger electrode sensors. Finally, we test our sensors over several concentrations to emulate the range of pancreatic secretions. Ultimately, our microsensor will serve as the foundation for developing in situ sensors toward diagnosing pancreatic pathologies. [ABSTRACT FROM AUTHOR]

The measurement and control of hydroxide ion (OH − ) concentration in solution are essential in industrial processes. However, no portable sensing method directly targeting OH − ion with low-cost has been reported till date. Herein, we demonstrate an electrical detection method for OH − concentration in solution based on impedance spectroscopy of hydroxyl ions (OH − ) attached to amorphous InGaZnO4 (aIGZO) film surfaces. The systematic examination of impedance response reveals that the resistance component of impedance is sensitive to the OH − ions interaction with the film surface. Results of X-ray photoemission spectroscopy confirm that the change of the impedance property is directly attributed to the amount of hydroxyl radical on the film surface originated from OH − ions in the solution. The impedance behavior of the film upon interaction with OH − was reasonably described by the theoretical analysis of optical measurements based on a vacancy-dependent model. Developed by applying this mechanism as a reference application, an easy-to-use aIGZO thin film based resistance OH − sensor at room temperature shows superior sensitivity, reproducibility, and linearity in the alkali range. This study extends the understanding and usage of aIGZO thin film regarding surface-sensing for the detection of surface interaction and process involving chemical ions and species. [ABSTRACT FROM AUTHOR]

Digestive health is critically dependent on the secretion of enzymes from the exocrine pancreas to the duodenum via the pancreatic duct. Specifically, pancreatic trypsin is a major protease responsible for breaking down proteins for absorption in the small intestine. Gelatin-based hydrogels, deposited in the form of thin films, have been studied as potential sensor substrates that hydrolyze in the presence of trypsin. In this work, we (1) investigate gelatin as a sensing material; (2) develop a fabrication strategy for coating sensor surfaces; and (3) implement a miniaturized impedance platform for measuring activity levels of pancreatic trypsin. Using impedance spectroscopy, we evaluate gelatin’s specificity and rate of degradation when exposed to a combination of pancreatic enzymes in neutral solution representative of the macromolecular heterogeneity present in the duodenal environment. Our findings suggest gelatin’s preferential degradation to trypsin compared to enzymes such as lipase and amylase. We further observe their interference with trypsin behavior in equivalent concentrations, reducing film digestion by as much as 83% and 77%, respectively. We achieve film patterns in thicknesses ranging from 300–700 nm, which we coat over interdigitated finger electrode sensors. Finally, we test our sensors over several concentrations to emulate the range of pancreatic secretions. Ultimately, our microsensor will serve as the foundation for developing in situ sensors toward diagnosing pancreatic pathologies.

Rapid tests to assess the susceptibility of bacteria to antibiotics are required to inform antibiotic stewardship. We have developed a novel test, which measures changes in the impedance of a 100 nanoliter volume of bacterial suspension to determine an "electrical" minimum inhibitory concentration (eMIC). Two representative strains of Klebsiella pneumoniae , Acinetobacter baumannii , Escherichia coli , Pseudomonas aeruginosa, and Staphylococcus aureus were tested against a panel of frontline antibiotics with different modes of action (ciprofloxacin, doxycycline, colistin and imipenem, gentamicin, and ceftazidime). The eMIC measured at 1 h correlated strongly with a standard 24 h microbroth dilution MIC for all combinations of antibiotics and bacteria, allowing strains to be correctly assigned as sensitive or resistant measured in a fraction of the time.

The principle of droplet-based microfluidics was used for the characterization of dose/response functions of the soil bacteria Rhodococcus sp. and Chromobacterium vaccinii using a combination of optical and electrical sensors for the detection of bacterial growth and metabolic activity. For electrical characterization, a micro flow-through impedance module was developed which assessed the response of bacterial populations inside 500 nL fluid segments without direct galvanic contact between the electrodes and the electrolyte. It was found that the impedance sensor can detect an increase in cell density and is particularly suited for monitoring the metabolic response due to changes in the cultivation medium inside the separated fluid segments. Due to this sensitivity, the sensor is useful for investigating growing bacteria or cell cultures in small fluid compartments and obtaining highly resolved dose-response functions by microfluid segment sequences. The impedimetric data agree well with the optical data concerning the characteristic response of bacteria populations in the different concentration regions of heavy metal ions. However, the sensor supplies valuable complementary data on metabolic activity in case of low or negligible cell division rates. [Display omitted] • Multichannel contactless microfluid optical and impedimetric sensing was developed. • Distinguish dose-response with the characteristic distribution of different measurement values. • Multi-sensor supplies valuable complementary data on metabolic activity. • Possibility to characterize the physiological activities of small cell populations and their response to chemical stress at an early stage of cultivation in nanoliter droplets. [ABSTRACT FROM AUTHOR]

A sensitive and rapid impedemetric immunosensor is demonstrated utilizing porous volumetric microfluidic detection elements and silver enhanced gold nanoparticle probes. The porous detection elements significantly increase capture probe density and decrease diffusion length scales compared to conventional planar sensors to improve target capture efficiency and enhance impedance signal. In this work, a packed bed of silica beads functionalized with antibody probes serves as a porous sensor element within a thermoplastic microchannel, with an interdigitated gold electrode microarray used to measure impedance changes caused by the concentration dependent formation of silver aggregates. The measured impedance change is independent of electrode spacing, enabling a device with low resolution electrodes to achieve a sandwich immunoassay detection limit between 1 and 10 ng/mL with a 4-log dynamic range, with a total assay time of 75 min. [ABSTRACT FROM AUTHOR]

In this manuscript, we present three different micro-impedance sensing architectures for electronic counting of cells and beads. The first method of sensing is based on using an open circuit sensing electrode integrated in a micro-pore, which measures the shift in potential as a micron-sized particle passes through. Our micro-pore, based on a funnel shaped microchannel, was fabricated in PDMS and was bound covalently to a glass substrate patterned with a gold open circuit electrode. The amplification circuitry was integrated onto a battery-powered custom printed circuit board. The second method is based on a three electrode differential measurement, which opens up the potential of using signal processing techniques to increase signal to noise ratio post measurement. The third architecture uses a contactless sensing approach, which significantly minimizes the cost of the consumable component of the impedance cytometer. We demonstrated proof of concept for the three sensing architectures by measuring the detected signal due to the passage of micron-sized beads through the pore. [ABSTRACT FROM AUTHOR]

Human airway epithelial cells express β-adrenergic receptors (β-ARs), which regulate mucociliary clearance by stimulating transepithelial anion transport and ciliary beat frequency. Previous studies using airway epithelial cells showed that stimulation with isoproterenol increased cell migration and wound repair by a cAMP-dependent mechanism. In the present study, impedance-sensing arrays were used to measure cell migration and epithelial restitution following wounding of confluent normal human bronchial epithelial (NHBE) and Calu-3 cells by electroporation. Stimulation with epinephrine or the β2-AR-selective agonist salbutamol significantly delayed wound closure and reduced the mean surface area of lamellipodia protruding into the wound. Treatment with the β-AR bias agonist carvedilol or isoetharine also produced a delay in epithelial restitution similar in magnitude to epinephrine and salbutamol. Measurements of extracellular signal-regulated kinase phosphorylation following salbutamol or carvedilol stimulation showed no significant change in the level of phosphorylation compared with untreated control cells. However, inhibition of protein phosphatase 2A activity completely blocked the delay in wound closure produced by β-AR agonists. In Calu-3 cells, where CFTR expression was inhibited by RNAi, salbutamol did not inhibit wound repair, suggesting that β-AR agonist stimulation and loss of CFTR function share a common pathway leading to inhibition of epithelial repair. Confocal images of the basal membrane of Calu-3 cells labeled with anti-β1-integrin (clone HUTS-4) antibody showed that treatment with epinephrine or carvedilol reduced the level of activated integrin in the membrane. These findings suggest that treatment with β-AR agonists delays airway epithelial repair by a G protein- and cAMP-independent mechanism involving protein phosphatase 2A and a reduction in β1-integrin activation in the basal membrane. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Humanized disease models are required to develop new therapies for currently incurable forms of AMD. In this work, a tissue-on-a-chip approach was developed through combining human induced pluripotent stem cells, Electric Cell–substrate Impedance Sensing (ECIS) and reproducible electrical wounding assays to model and quantitatively study AMD. Retinal Pigment Epithelium (RPE) cells generated from a patient with an inherited macular degeneration and from an unaffected sibling were used to test the model platform on which a reproducible electrical wounding assay was conducted to model RPE damage. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on the microelectrode arrays. A spatially controlled RPE layer damage that mimicked cell loss in AMD disease was then initiated. Post recovery, significant differences ( P <0.01) in migration rates were found between case (8.6±0.46 μm/h) and control cell lines (10.69±0.21 μm/h). Quantitative data analysis suggested this was achieved due to lower cell–substrate adhesion in the control cell line. The ECIS cell–substrate adhesion parameter ( α ) was found to be 7.8±0.28 Ω 1/2 cm for the case cell line and 6.5±0.15 Ω 1/2 cm for the control. These findings were confirmed using cell adhesion biochemical assays. The developed disease model-on-a-chip is a powerful platform for translational studies with considerable potential to investigate novel therapies by enabling real-time, quantitative and reproducible patient-specific RPE cell repair studies. [ABSTRACT FROM AUTHOR]

Impedance sensing, together with impedance spectroscopy is a powerful tool detecting charge and mass transfer phenomena at complex interfaces between materials. It is widely used in electrochemical interfaces characterization and biosensing techniques. Recently, it has been proposed as a reliable readout technique to probe biomolecular interactions on modified electrodes in enzyme biosensors, DNA biosensors and immunosensors. Unfortunately, the requirements of impedance characterization accuracy, precision and dynamic range demanded by some specific application is usually accomplished by using cumbersome laboratory instrumentation. In this paper we present a fully integrated standalone, high precision, low power, 4-core impedance sensing interface to be implemented in the fast-growing application field of the ubiquitous sensing. The interface is based on a fully digital approach based on a ΔΣ demodulation that is able to achieve 15 bit of resolution, 150 ppm of temperature accuracy and dynamic ranges varying from 86 dB to 95 dB according to the impedance configuration. The 4-core chip has been implemented in 0.35 µm CMOS technology and occupies an area of 9 mm^2. [ABSTRACT FROM AUTHOR]

This article presents a miniature haptic actuator (or haptic button) based on magneto-rheological fluids, designed to convey realistic and vivid haptic sensations to users in small electronic devices. The haptic sensation, which is generated in the form of resistive force, should vary according to the stroke of the actuator (or the pressed depth of its plunger). Thus, a sensing method for gauging the stroke should be integrated into the proposed magneto-rheological actuator to demonstrate real-world haptic applications. To determine the pressed depth of the magneto-rheological actuator, this article proposes an impedance sensing mechanism. The proposed sensing method measures the impedance change of the solenoid coil built in the actuator in the form of voltages to estimate the pressed depth. A control system was constructed to evaluate the simultaneous sensing and actuating performance of the proposed. The results show that the sensitivity of the proposed sensing method is sufficient to regulate the output resistive force over the small stroke range of the actuator. The results further show that the controller with the proposed sensing method enables users to measure the displacement of the plunger and concurrently generate resistive forces to convey haptic sensations to users without additional sensors. [ABSTRACT FROM AUTHOR]

This work presents a module-level impedance measurement system integrated with a disposable immunosensor for the immunoassay of bladder cancer cell lysate (T24) to a specific antibody (galectin-1). The immunosensor consisted of a flexible printed circuit patterned with an interdigital microelectrode array which immobilized polyaniline-modified nanoprobes on an electrode surface by dielectrophoresis. A quantitative sampling of cell lysate without a pump was made by using paper as the cell lysate carrier and sweeping a moistened paper over the sensing area of interdigital microelectrode array for sampling. In this study, the impedance measurement results of the module-level system were compared with those measured by the precision LCR meter, in which the error is <2 %. Additionally, the normalized impedance variation in immunosensing linearly increased with the cell lysate concentration. With a sensitivity based on a normalized impedance variation of 124.4 % per mg/ml, the immunosensor can rapidly detect the lowest concentration of cell lysate for 0.0626 mg/ml in 10 min. Therefore, this work has demonstrated the accuracy of the module-level immunosensor as well as the reliability of impedance-based sensing for bladder cancer cell lysate. The proposed disposable sensor and portable impedance system module are highly promising for use in point-of-care diagnostics. [ABSTRACT FROM AUTHOR]

Low-cost detection of pathogens and biomolecules at the point-of-care promises to revolutionize medicine through more individualized monitoring and increased accessibility to diagnostics in remote and resource-limited areas. While many approaches to biosensing are still limited by expensive components or inadequate portability, we present here an ELISA-inspired lab-on-a-chip strategy for biological detection based on liposome tagging and ion-release impedance spectroscopy. Ion-encapsulating dipalmitoylphosphatidylcholine (DPPC) liposomes can be functionalized with antibodies and are stable in deionized water yet permeabilized for ion release upon heating, making them ideal reporters for electrical biosensing of surface-immobilized antigens. We demonstrate the quantification of these liposomes by real-time impedance measurements, as well as the qualitative detection of viruses as a proof-of-concept toward a portable platform for viral load determination which can be applied broadly to the detection of pathogens and other biomolecules. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cell growth and metabolism were continuously and synchronously monitored by cellular impedance sensing and LAPS based on the same sensor structure. [•] Electrolyte-insulator-semiconductor (EIS) structure was used as the sensor structure. [•] Equivalent circuit model for cellular impedance sensing was build. [•] Cytotoxicity of heavy metal Cadmium (Cd) was evaluated. [Copyright &y& Elsevier]