Accurate and reliable measurement of the electrical impedance spectrum is an essential requirement in order to draw relevant conclusions in many fields and a variety of applications; in particular, for biological processes Even in the state-of-the-art methods developed for this purpose, the accuracy and efficacy of impedance measurements are reduced in biological systems, due to the regular occurrence of parameters causing measurement errors such as residual impedance, parasitic capacitance, generator anomalies, and so on Recent observations have reported the necessity of decreasing such inaccuracies whenever measurements are performed in the ultra-low frequency range, as the above-mentioned errors are almost entirely absent in such cases The current research work proposes a method which can reject the anomalies listed above when measuring in the ultra-low frequency range, facilitating data collection at the same time To demonstrate our hypothesis, originating from the consideration of the determinant role of the measuring frequency, a physical model is proposed to examine the effectiveness of our method by measuring across the commonly used vs ultra-low frequency ranges Validation measurements reflect that the range of frequencies and the accuracy is much greater than in state-of-the-art methods Using the proposed new impedance examination technique, biological system characterization can be carried out more accurately

Physical Validation of a Residual Impedance Rejection Method during Ultra-Low Frequency Bio-Impedance Spectral Measurements.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, it is the primary cause of liver-related morbidity and mortality. The prevalence of the disease is estimated as high as 25% of the general population up to 90% of obese and diabetic patients. Most patients are asymptomatic or does not experience specific complaints making them difficult to diagnose and treat. However, due to the limitations of available diagnostic procedures and the current gold standard for diagnosis, the liver biopsy, there is a worldwide demand to develop a non-invasive diagnostic tool and procedure that can detect the disease with high accuracy at an early reversible stage, furthermore is cost-effective, user-friendly, and provides repeatable measurement. Based on the metrological experience of our research team, we started developing an electrical impedance-based diagnostic procedure a few years ago that meets these requirements and is suitable for early detection of NAFLD with the help of a world-new measurement and data collection solution. In this article, we present the most important milestones in the development of instruments related to research.

Development of Bioimpedance-based Measuring Systems for Diagnosis of Non-alcoholic Fatty Liver Disease

The oxygen plays an important role in the development and function of the human brain. In the central nervous system, a different neuron types can be very sensitive to varying concentrations of oxygen. Despite several cell biology researches, the time course of the effects of non-physiological oxygen concentrations, but especially high oxygen concentrations on the membrane of neurons, and the dynamics of damage are unknown. In the present study, with this in view, electrical impedance spectroscopy (EIS) measurements are carried out using a graphene-based self-developed four-electrode measurement and data collection process. Our goal was to produce a plate layout for our further experiments that could be used to examine cell cultures under hypoxic and hyperoxic conditions. The designs differ in the distance between the electrodes, we used three types of distances: 1 mm, 3 mm 5 mm, using one distance per plate. On the plate with 5 mm electrode spacing we found the ideal. From a measurement point of view, the plate with 5 mm electrode spacing was the most suitable. As we increased the distance, the size of the electrode surfaces decreased. It can be assumed that reducing the size of the electrodes did not negatively affect the measurement results. Our results can greatly contribute to better understand the process of cell membrane damage.

Development of a Bioimpedance Measuring Plate for the Study of Hypoxic and Hyperoxic Conditions in Cell Cultures

Nowadays, the gold standard for the diagnosis of liver disease is histological examination. However, due to the dangers and complications of liver biopsy, there is a worldwide demand for the development of non-invasive procedures that can accurately determine the degree of hepatic steatosis, furthermore is cost-effective, user-friendly, and provides repeatable measurement. Based on the metrological experience of our research team, we started developing an electrical impedance-based diagnostic method a few years ago that meets these requirements and is suitable for early detection of nonalcoholic fatty liver disease (NAFLD) with the help of a worldnew measurement and data collection solution. In addition to the preliminar results of the long-term clinical validation of the diagnostic method developed to detect NAFLD, the authors present early partial results. Even with the small amount of data, very impressive results have been obtained.

Proof of Concept Clinical Trial of Bioimpedance-based NAFLD Diagnosis Technique

Based on a prior university patent, the authors developed a novel type of bioimpedance-based test method to noninvasively detect nonalcoholic fatty liver disease (NAFLD). The development of a new potential NAFLD diagnostic procedure may help to understand the underlying mechanisms between NAFLD and severe liver diseases with a painless and easy-to-use paraclinical examination method, including the additional function to detect even the earlier stages of liver disease. The aim of this study is to present new results and the experiences gathered in relation to NAFLD progress during animal model and human clinical trials. 

Novel Noninvasive Paraclinical Study Method for Investigation of Liver Diseases

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Physical Validation of a Residual Impedance Rejection Method during Ultra-Low Frequency Bio-Impedance Spectral Measurements.