Microelectrode arrays (MEA) record extracellular local field potentials of cells adhered to the electrodes. A disadvantage is the limited signal-to-noise ratio. The state-of-the-art background noise level is about 10 μVpp. Furthermore, in MEAs low frequency events are filtered out. Here, we quantitatively analyze Au electrode/electrolyte interfaces with impedance spectroscopy and noise measurements. The equivalent circuit is the charge transfer resistance in parallel with a constant phase element that describes the double layer capacitance, in series with a spreading resistance. This equivalent circuit leads to a Maxwell-Wagner relaxation frequency, the value of which is determined as a function of electrode area and molarity of an aqueous KCl electrolyte solution. The electrochemical voltage and current noise is measured as a function of electrode area and frequency and follow unambiguously from the measured impedance. By using large area electrodes the noise floor can be as low as 0.3 μVpp. The resulting high sensitivity is demonstrated by the extracellular detection of C6 glioma cell populations. Their minute electrical activity can be clearly detected at a frequency below about 10 Hz, which shows that the methodology can be used to monitor slow cooperative biological signals in cell populations.
aeMeasuring the electrical activity of large and defined populations of cells is currently a major technical challenge to electrophysiology, especially in the picoampere-range. For this purpose, we developed and applied a bidirectional transducer based on a chip with interdigitated gold electrodes to record the electrical response of cultured glioma cells. Recent research determined that also non-neural brain glia cells are electrically active and excitable. Their transformed counterparts, e.g. glioma cells, were suggested to partially retain these electric features. Such electrophysiological studies however are usually performed on individual cells and are limited in their predictive power for the overall electrical activity of the multicellular tumour bulk. Our extremely low-noise measuring system allowed us to detect not only prominent electrical bursts of neuronal cells but also minute, yet constantly occurring and functional, membrane capacitive current oscillations across large populations of C6 glioma cells, which we termed electric current noise.At the same time, tumour cells of non-brain origin (HeLa) proved to be electrically quiescent in comparison.Finally, we determined that the glioma cell activity is primarily caused by the opening of voltage-gated Na + and K + ion channels and can be efficiently abolished using specific pharmacological inhibitors. Thus, we offer here a unique approach for studying electrophysiological properties of large cancer cell populations as an in vitro reference for tumour bulks in vivo.
Extracellular electrode recording demonstrates acid-triggered electrical activity in glioma cell populations.
A deeper understanding of the influence of common cardiovascular diseases like stenosis, aneurysm or atherosclerosis on the circulatory mechanism is required, to establish new methods for early diagnosis. Different types of simulators were developed in the past to simulate healthy and pathological conditions of blood flow, often based on computational models, which allow to generate large data sets. However, since computational models often lack some aspects of real world data, hardware simulators are used to close this gap and generate data for model validation. The aim of this study is the development and validation of a hardware simulator to generate benchmark data sets of healthy and pathological conditions. The in-vitro hardware simulator in this study includes the major 33 arteries and is driven by a ventricular assist device generating a parametrised input condition at the heart node. Physiologic flow conditions including heart rate, systolic/diastolic pressure, peripheral resistance and compliance are adjustable in a wide range. The pressure and flow waves at 17+1 different locations are measured by inverted fluid resistant pressure transducers and one ultrasound flow transducer supporting a detailed analysis of the measurement data. The pressure and flow waves show physiological conditions. Furthermore, the influence of stenoses degree and location on blood pressure and flow was investigated. The results indicate decreasing translesional pressure and flow with increasing degree of stenosis, as expected. The benchmark data set is made available to the research community, with the purpose to validate and compare in-silico models of different type.
Cardiovascular diseases are commonly caused by atherosclerosis, stenosis and aneurysms. Understanding the influence of these pathological conditions on the circulatory mechanism is required to establish methods for early diagnosis. Different tools have been developed to simulate healthy and pathological conditions of blood flow. These simulations are often based on computational models that allow the generation of large data sets for further investigation. However, because computational models often lack some aspects of real-world data, hardware simulators are used to close this gap and generate data for model validation. The aim of this study is to develop and validate a hardware simulator to generate benchmark data sets of healthy and pathological conditions. The development process was led by specific design criteria to allow flexible and physiological simulations. The in vitro hardware simulator includes the major 33 arteries and is driven by a ventricular assist device generating a parametrised in-flow condition at the heart node. Physiologic flow conditions, including heart rate, systolic/diastolic pressure, peripheral resistance and compliance, are adjustable across a wide range. The pressure and flow waves at 17+1 locations are measured by inverted fluid-resistant pressure transducers and one ultrasound flow transducer, supporting a detailed analysis of the measurement data even for in silico modelling applications. The pressure and flow waves are compared to in vivo measurements and show physiological conditions. The influence of the degree and location of the stenoses on blood pressure and flow was also investigated. The results indicate decreasing translesional pressure and flow with an increasing degree of stenosis, as expected. The benchmark data set is made available to the research community for validating and comparing different types of computational models. It is hoped that the validation and improvement of computational simulation models will provide better clinical predictions.
Glioblastoma, an aggressive malign tumor of the brain, is one of the most shattering diagnoses due to its very poor prognosis and limited treatment options. These options mainly consist of surgical or radiation therapeutic removal of as much tumor mass as possible, which unfortunately is almost always incomplete. Even worse, chemotherapy is of little use, as the special setup of the brain′s vessels severely limits the transit into the parenchyma of elsewhere efficient cytostatica. This Blood-Brain-Barrier (BBB) is for quite some time the target of sophisticated and nano-particle based transport mechanisms, however it is reported, that a boost of permeability for most of the brain can be achieved based on moderate temperature increase. One means to locally and reversibly increase the brain′s temperature and thus potentially opening the BBB may be achieved by illuminating the skull with infrared laser light, thus causing punctual heating and heat diffusion into the cortex. In extension of the common laser light guiding by glass fibres, we use a micro-positioned simple optics to focus a 1470 nm laser beam of approximately 500 µm in diameter on the skull. The apparent opening of the BBB is evidenced by the localized spread of Evans Blue injected into the tail vein of said rat, binding to Albumin (64,6 kDa) in the body. This marker molecule is usually blocked from passing through the intact BBB, but under IR illumination for half a minute, it appeared in post mortem visible blobs. Temperature profiles and potential tissue damage are now under investigation by high speed thermal camera and post mortem histology.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.