A new label free spiral sensor using impedance spectroscopy to characterize hepatocellular carcinoma in tissue and serum samples.

Hepatocellular carcinoma (HCC) stands as the most prevalent form of primary liver cancer, predominantly affecting patients with chronic liver diseases such as hepatitis B or C-induced cirrhosis. Diagnosis typically involves blood tests (assessing liver functions and HCC biomarkers), imaging procedures such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), and liver biopsies requiring the removal of liver tissue for laboratory analysis. However, these diagnostic methods either entail lengthy lab processes, require expensive imaging equipment, or involve invasive techniques like liver biopsies. Hence, there exists a crucial need for rapid, cost-effective, and noninvasive techniques to characterize HCC, whether in serum or tissue samples. In this study, we developed a spiral sensor implemented on a printed circuit board (PCB) technology that utilizes impedance spectroscopy and applied it to 24 tissues and sera samples as proof of concept. This newly devised circuit has successfully characterized HCC and normal tissue and serum samples. Utilizing the distinct dielectric properties between HCC cells and serum samples versus the normal samples across a specific frequency range, the differentiation between normal and HCC samples is achieved. Moreover, the sensor effectively characterizes two HCC grades and distinguishes cirrhotic/non-cirrhotic samples from tissue specimens. In addition, the sensor distinguishes cirrhotic/non-cirrhotic samples from serum specimens. This pioneering study introduces Electrical Impedance Spectroscopy (EIS) spiral sensor for diagnosing HCC and liver cirrhosis in clinical serum-an innovative, low-cost, rapid (< 2 min), and precise PCB-based technology without elaborate sample preparation, offering a novel non-labeled screening approach for disease staging and liver conditions.

Optimization design of interdigitated microelectrodes with an insulation layer on the connection tracks to enhance efficiency of assessment of the cell viability.

BACKGROUND: Microelectrical Impedance Spectroscopy (µEIS) is a tiny device that utilizes fluid as a working medium in combination with biological cells to extract various electrical parameters. Dielectric parameters of biological cells are essential parameters that can be extracted using µEIS. µEIS has many advantages, such as portability, disposable sensors, and high-precision results. RESULTS: The paper compares different configurations of interdigitated microelectrodes with and without a passivation layer on the cell contact tracks. The influence of the number of electrodes on the enhancement of the extracted impedance for different types of cells was provided and discussed. Different types of cells are experimentally tested, such as viable and non-viable MCF7, along with different buffer solutions. This study confirms the importance of µEIS for in vivo and in vitro applications. An essential application of µEIS is to differentiate between the cells' sizes based on the measured capacitance, which is indirectly related to the cells' size. The extracted statistical values reveal the capability and sensitivity of the system to distinguish between two clusters of cells based on viability and size. CONCLUSION: A completely portable and easy-to-use system, including different sensor configurations, was designed, fabricated, and experimentally tested. The system was used to extract the dielectric parameters of the Microbeads and MCF7 cells immersed in different buffer solutions. The high sensitivity of the readout circuit, which enables it to extract the difference between the viable and non-viable cells, was provided and discussed. The proposed system can extract and differentiate between different types of cells based on cells' sizes; two other polystyrene microbeads with different sizes are tested. Contamination that may happen was avoided using a Microfluidic chamber. The study shows a good match between the experiment and simulation results. The study also shows the optimum number of interdigitated electrodes that can be used to extract the variation in the dielectric parameters of the cells without leakage current or parasitic capacitance.

Theoretical analysis for the fluctuation in the electric parameters of the electroporated cells before and during the electrofusion.

An electric pulse with a sufficient amplitude can lead to electroporation of intracellular organelles. Also, the electric field can lead to electrofusion of the neighboring cells. In this paper, a finite element mathematical model was used to simulate the distribution, radius, and density of the pores. We simulated a mathematical model of the two neighbor cells to analyze the fluctuation in the electroporation parameters before the electrofusion under the ultra-shorted electric field pulse (i.e., impulse signal) for each cell separately and after the electrofusion under the ultra-shorted pulse. The analysis of the temporal and spatial distribution can lead to improving the mathematical models that are used to analyze both electroporation and electrofusion. The study combines the advantages of the nanosecond pulse to avoid the effect of the cell size on the electrofusion and the large-pore radius at the contact point between the cells.

CMOS based capacitive sensor matrix for characterizing and tracking of biological cells.

The characterization and tracking of biological cells using biosensors are necessary for many scientific fields, specifically cell culture monitoring. Capacitive sensors offer a great solution due to their ability to extract many features such as the biological cells' position, shape, and capacitance. Through this study, a CMOS-based biochip that consists of a matrix of capacitive sensors (CSM), utilizing a ring oscillator-based pixel readout circuit (PRC), is designed and simulated to track and characterize a single biological cell based on its aforementioned different features. The proposed biochip is simulated to characterize a single Hepatocellular carcinoma cell (HCC) and a single normal liver cell (NLC). COMSOL Multiphysics was used to extract the capacitance values of the HCC and NLC and test the CSM's performance at different distances from the analyte. The PRC's ability to detect the extracted capacitance values of the HCC and NLC is evaluated using Virtuoso Analog Design Environment. A novel algorithm is developed to animate and predict the location and shape of the tested biological cell depending on CSM's capacitance readings simultaneously using MATLAB R2022a script. The results of both models, the measured capacitance from CSM and the correlated frequency from the readout circuit, show the biochip's ability to characterize and distinguish between HCC and NLC.

Adipose Stem Cells Display Higher Regenerative Capacities and More Adaptable Electro-Kinetic Properties Compared to Bone Marrow-Derived Mesenchymal Stromal Cells.

Adipose stem cells (ASCs) have recently emerged as a more viable source for clinical applications, compared to bone-marrow mesenchymal stromal cells (BM-MSCs) because of their abundance and easy access. In this study we evaluated the regenerative potency of ASCs compared to BM-MSCs. Furthermore, we compared the dielectric and electro-kinetic properties of both types of cells using a novel Dielectrophoresis (DEP) microfluidic platform based on a printed circuit board (PCB) technology. Our data show that ASCs were more effective than BM-MSCs in promoting neovascularization in an animal model of hind-limb ischemia. When compared to BM-MSCs, ASCs displayed higher resistance to hypoxia-induced apoptosis, and to oxidative stress-induced senescence, and showed more potent proangiogenic activity. mRNA expression analysis showed that ASCs had a higher expression of Oct4 and VEGF than BM-MSCs. Furthermore, ASCs showed a remarkably higher telomerase activity. Analysis of the electro-kinetic properties showed that ASCs displayed different traveling wave velocity and rotational speed compared to BM-MSCs. Interestingly, ASCs seem to develop an adaptive response when exposed to repeated electric field stimulation. These data provide new insights into the physiology of ASCs, and evidence to their potential superior potency compared to marrow MSCs as a source of stem cells.