This paper presents the fabrication and testing of a novel stretchable electric cell–substrate impedance sensing (ECIS) lab on a chip device. This is the first time that ECIS electrodes were fabricated on a stretchable polydimethylsiloxane (PDMS) substrate and ECIS measurements were performed on mammalian cells exposed to cyclic strain. The stretchable ECIS biosensors simulate in vitro the dynamic environment of organisms, such as pulsation, bending and stretching, which enables investigations on cell behavior that undergoes mechanical stimuli in biological tissue. Usually cell-based assays used in cell mechanobiology rely on endpoint cell tests, which provide a limited view on dynamic cellular mechanisms. The ECIS technique is a label-free, real-time and noninvasive method to monitor the cellular response to mechanical stimuli. Bovine aortic endothelial cells (BAECs) have been used in this research because the BAECs are exposed in vivo to cyclic physiologic elongation produced by blood circulation in the arteries. These innovative stretchable ECIS biosensors were used to analyze the proliferation of BAECs under different cyclic mechanical stimulations. The results of fluorescence based cell proliferation assays confirmed that the stretchable ECIS sensors were able to analyze in real-time the BAEC proliferation. The novel stretchable ECIS sensor has the ability to analyse cell proliferation, determine the cell number and density, and apply mechanical stimulation at the same time.
A novel multiparametric biosensor system based on living cells will be presented. The biosensor system includes two biosensing techniques on a single device: resonant frequency measurements and electric cell-substrate impedance sensing (ECIS). The multiparametric sensor system is based on the innovative use of the upper electrode of a quartz crystal microbalance (QCM) resonator as working electrode for the ECIS technique. The QCM acoustic wave sensor consists of a thin AT-cut quartz substrate with two gold electrodes on opposite sides. For integration of the QCM with the ECIS technique a semicircular counter electrode was fabricated near the upper electrode on the same side of the quartz crystal. Bovine aortic endothelial live cells (BAECs) were successfully cultured on this hybrid biosensor. Finite element modeling of the bulk acoustic wave resonator using COMSOL simulations was performed. Simultaneous gravimetric and impedimetric measurements performed over a period of time on the same cell culture were conducted to validate the device’s sensitivity. The time necessary for the BAEC cells to attach and form a compact monolayer on the biosensor was 35~45 minutes for 1.5 × 104 cells/cm2 BAECs; 60 minutes for 2.0 × 104 cells/cm2 BAECs; 70 minutes for 3.0 × 104 cells/cm2 BAECs; and 100 minutes for 5.0 × 104 cells/cm2 BAECs. It was demonstrated that this time is the same for both gravimetric and impedimetric measurements. This hybrid biosensor will be employed in the future for water toxicity detection.
This review paper is focused on various applications of electric cellsubstrate impedance sensing (ECIS) using adherent, two-dimensional (2D) mammalian cell culture. The ECIS technique is a non-destructive electrical approach to in vitro monitor in continuous fashion and real time the cell behavior related to attachment, growth, morphology, motility, proliferation and viability. The use of living cells as sensorial elements provides the opportunity for analysis of a large variety of pharmaceutical compounds and toxicants that affect cellular responses. In this review, we will cover some of the most important applications of the ECIS technique such as: impedance of cancer cell, toxicity studies, and investigation of stem cell using impedance spectroscopy sensing. Contractile activity of beating cardiomyocytes recorded with ECIS will also be presented. Combination of impedance sensing and resonant frequency measurements of cell monolayer will be discussed. An innovative stretchable device with integrated ECIS electrodes will be discussed. Recently, the ECIS technique was combined with machine learning algorithms to distinguish stem cell proliferation from the differentiation processes. This review demonstrates that ECIS is a powerful tool, effective to investigate mammalian cell properties and physiological functions and provides advantages over conventional assays, including simple, rapid and noninvasive cell screening.
The paper describes a stretchable, microfabricated power generator that will be attached on the skin and will produce energy based on the movements of the human body. The device was fabricated on a polymeric, elastomeric, poly(dimethylsiloxane) (PDMS) sheet. It consists of a piezoelectric thin film of ZnO sandwiched between two stretchable gold electrodes. An innovative technique was used for the deposition of ZnO thin film on the gold electrode-coated polymeric substrate at low temperatures below 150 °C. This is the first attempt to use a uniform film of ZnO, for energy harvesting. The ZnO film had the thickness at the submicron scale and the surface at the centimeter scale. We demonstrated that under a strain of 8% the voltage output from this power generator was equal to 2 V, the power output was equal to 160 μW and the corresponding power density was 1.27 mW/cm2. This device has great potential for application in power sensors attached on the human body, such as temperature sensors or wearable electrocardiography systems.
This review presents several sensors with dimensions at the nano- and micro-scale used for biological applications. Two types of cantilever beams employed as highly sensitive temperature sensors with biological applications will be presented. One type of cantilever beam is fabricated from composite materials and is operated in the deflection mode. In order to achieve the high sensitivity required for detection of heat generated by a single mammalian cell, the cantilever beam temperature sensor presented in this review was microprocessed with a length at the microscale and a thickness in the nanoscale dimension. The second type of cantilever beam presented in this review was operated in the resonant frequency regime. The working principle of the vibrating cantilever beam temperature sensor is based on shifts in resonant frequency in response to temperature variations generated by mammalian cells. Besides the cantilever beam biosensors, two biosensors based on the electric cell-substrate impedance sensing (ECIS) used to monitor mammalian cells attachment and viability will be presented in this review. These ECIS sensors have dimensions at the microscale, with the gold films used for electrodes having thickness at the nanoscale. These micro/nano biosensors and their mammalian cell applications presented in the review demonstrates the diversity of the biosensor technology and applications.
Starting from solid-solutions (SS) of AlCoCrFeNix high-entropy alloys (HEAs) that have been produced with high purity constituent elements by vacuum arc remelting (VAR) method varying the nickel molar ratio x from 0.2 to 2.0, we investigated the synthesis of protective thin films of HEAs and high-entropy nitrides (HENs) with the aid of the pulsed laser deposition (PLD) system. The structure of all ten available bulk targets have been examined by means of X-Ray Diffraction (XRD), as well as their elemental composition by means of energy dispersion X-ray spectroscopy (EDS). Three targets with nickel molar composition x = 0.4, 1.2 and 2.0 corresponding to BCC, mixed BCC and FCC, and finally FCC structures were used for thin film depositions using a KrF excimer laser. The depositions were performed in residual low vacuum (10−7 mbar) and under N2 (10−4 mbar) at room temperature (RT~25 °C) on Si and glass substrates. The deposited films’ structure was investigated using grazing incidence XRD, their surface morphology, thickness and elemental composition by scanning electron microscopy (SEM), EDS and X-ray photoelectron spectroscopy (XPS), respectively. A homemade four-point probe (4PP) set-up was applied to determine layers electrical resistance. Besides, a Nanoindentation (NI) was employed to test films’ mechanical properties. XRD results showed that all deposited films, regardless of the initial structure of targets, were a mixture of FCC and BCC structures. Additionally, the quantitative and qualitative EDS and XPS results showed that the elemental composition of films was rather close to that of the targets. The depositions under an N2 atmosphere resulted in the inclusion of several percentage nitrogen atoms in a metallic nitride type compound into films, which may explain their higher electrical resistivity. The Young’s modulus, nanohardness and friction coefficient values showed that the deposited films present good mechanical properties and could be used as protective coatings to prevent damage in harsh environments.