Assay based on electrical impedance spectroscopy to discriminate between normal and cancerous mammalian cells

In this work we present an assay to discriminate between normal and cancerous cells. The method is based on the measurement of electrical impedance spectra of in vitro cell cultures. We developed a protocol consisting on four consecutive measurement phases, each of them designed to obtain different information about the cell cultures. Through the analysis of the measured data, 26 characteristic features were obtained for both cell types. From the complete set of features, we selected the most relevant in terms of their discriminant capacity by means of conventional statistical tests. A linear discriminant analysis was then carried out on the selected features, allowing the classification of the samples in normal or cancerous with 4.5% of false positives and no false negatives.Fil: Giana, Fabián Eduardo. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Bonetto, Fabian Jose. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Bellotti, Mariela. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentin

Design and testing of a microelectrode array with spatial resolution for detection of cancerous cells in mixed cultures

We present the design, construction and testing of a microelectrode array with spatial resolution which can be used for the detection of cancerous cells in a mixed cell culture by means of the impedance spectroscopy technique. Two different microelectrode diameters, namely 57 m and 211 m, were tested. A layer of an AuCu alloy was deposited between the glass substrate and the exterior Au layer, enhancing the adhesion of the microelectrodes to the substrate and at the same time showing lower impedance than the commonly used material Au. Characteristic features were extracted from the impedance measurements at different phases (growth, confluence, wound and healing) and used to feed a Linear Discriminant Analysis algorithm in order to discriminate between normal and cancerous cells. Relevant statistical tests were applied in the discrimination model for each phase. Finally, it was determined that the larger microelectrodes have a superior discriminant capacity: no incorrect classifications were obtained with microelectrodes measuring 211 m in diameter, while 23.5% false positives and 5.6% false negatives were obtained with 57 m microelectrodes.Fil: Giana, Fabián Eduardo. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bonetto, Fabian Jose. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bellotti, M. I.. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentin

A new technique to detect ocular pathologies based on electrical measurement implemented on programmable logic

We developed a technique that detects superficial ocular pathologies based on the measurement of electrical impedance spectra. The sensor used is a small microelectrode made of platinum insulated from a cylindrical counterelectrode built of surgical stainless steel. The sensor has the shape of a truncated cone made of acrylic with dimensions identical to that of a standard Goldman prism. The sensor is applied to normal and pathological subject eyes with a constant force provided by a commercial tonometer. The circuit is closed through the lacrimal layer and the epithelial and endothelial cells. We measure the electrical impedance with a programmable logic device in which we implemented all the significant functions. These are the synthesis of the seventeen sines for the excitation, one lock-in, and delta-sigma modulators for the digital-to-analog converter and analog-to-digital converter requirements. A simple analog circuit filters the output, implements a voltage divider, and acts as current limiter in order not to damage the cells. We convert the measurements to resistance and capacitance as a function of frequencies. Consistent results are obtained for left and right eyes of the normal subjects. Significant differences are detected between the results for normal eyes and pathological eyes.Fil: Bellotti, Mariela I.. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; ArgentinaFil: Dellavale Clara, Hector Damian. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Bonetto, Fabian Jose. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentin

Positional stability and radial dynamics of sonoluminescent bubbles under bi-harmonic driving: Effect of the high-frequency component and its relative phase

The use of bi-frequency driving in sonoluminescence has proved to be an effective way to avoid the spatial instability (pseudo-orbits) developed by bubbles in systems with high viscous liquids like sulfuric or phosphoric acids. In this work, we present extensive experimental and numerical evidence in order to assess the effect of the high frequency component (PAcHF) of a bi-harmonic acoustic pressure field on the dynamic of sonoluminescent bubbles in an aqueous solution of sulfuric acid. The present study is mainly focused on the role of the harmonic frequency (Nf0) and the relative phase between the two frequency components (φb) of the acoustic field on the spatial, positional and diffusive stability of the bubbles. The results presented in this work were analyzed by means of three different approaches. First, we discussed some qualitative considerations about the changes observed in the radial dynamics, and the stability of similar bubbles under distinct bi-harmonic drivings. Later, we have investigated, through a series of numerical simulations, how the use of high frequency harmonic components of different order N, affects the positional stability of the SL bubbles. Furthermore, the influence of φb in their radius temporal evolution is systematically explored for harmonics ranging from the second to the fifteenth harmonic (N=2-15). Finally, a multivariate analysis based on the covariance method is performed to study the dependences among the parameters characterizing the SL bubble. Both experimental and numerical results indicate that the impact of PAcHF on the positional instability and the radial dynamics turns to be progressively negligible as the order of the high frequency harmonic component grows (i.e. N1), however its effectiveness on the reduction of the spatial instability remains unaltered or even improved.Fil: Rosselló, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Dellavale Clara, Hector Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche). División Bajas Temperaturas; ArgentinaFil: Bonetto, Fabian Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentin

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Abstract: Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders

On the stability of the point reactor kinetics equations

As the basic neutronic problem is unstable by nature, maintaining a reactor critical is a task that requires a lot of effort. This work presents and discusses some aspects related to the stability of the basic physics behind a nuclear reactor core based on the well-known point reactor kinetics equations. First, the linear non-feedback case is studied where differences between Lyapunov and BIBO stability are found. These differences are shown both numerically and analytically, and explained using a reactor physics based reasoning. Finally, a simple model is used to analyse the intrinsic stability of the point reactor equations when reactivity feedbacks are taken into account. A method for constructing conceptual stability design maps is proposed and a basic interpretation of the simple results obtained is given.Fil: Theler, Germán G.. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Tecna S. A.; ArgentinaFil: Bonetto, Fabian Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Tecna S. A.; Argentin

A novel water hammer device designed to produce controlled bubble collapses

In this work, a novel prototype of a water hammer device designed to produce controlled collapses of a single cavitation bubble is presented. It employs a new driving method in which a laser generated bubble is initially expanded and subsequently compressed using an electromechanical piston. It brings the possibility of reaching high energy concentrations in the collapses and allows the independent control of the most relevant system parameters. In this way, a higher control over the bubble dynamics is obtained compared to the typically reported in acoustically driven systems, laser cavitation or a conventional water hammer. This device constitutes a proof of concept in a series of low energy trials performed using glycerin and phosphoric acid as working liquids. Simulations of the bubble dynamics for prototypical cases were performed in order to extend the experimental results. We found that the most relevant parameter related to collapse strength is the expansion ratio, i.e. the radius of the expanded bubble (before compression) over the equilibrium bubble radius. The results clearly indicate that this driving strategy has a great potential to produce high energy bubble collapses.Fil: Rosselló, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Urteaga, Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Física del Litoral. Universidad Nacional del Litoral. Instituto de Física del Litoral; ArgentinaFil: Bonetto, Fabian Jose. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentin

High-frequency Digital Lock-in Amplifier Using Random Sampling

A high-frequency digital lock-in amplifier (LIA) that uses a random-sampling scheme is proposed and tested experimentally in this paper. By using this sampling strategy, it is possible to process, without aliasing effects, periodic signals of frequencies that are several times higher than the Nyquist frequency. Analytical and numerical analyses that show the advantages and limitations of the proposed scheme are presented. A high-frequency digital LIA implementation is also described. The prototype maximum sampling frequency is 150 kHz, and its maximum signal frequency without aliasing is 2.5 MHz, limited only by the random-sampling period quantization. Experimental results that validate the proposal are presented.Fil: Sonnaillon, Maximiliano Osvaldo. Comision Nacional de Energia Atomica. Fundación Jose A. Balseiro; ArgentinaFil: Urteaga, Raul. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bonetto, Fabian Jose. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Impedance spectroscopy applied to the fast wounding dynamics of an electrical wound-healing assay in mammalian cells

Electrical wound-healing assays are often used as a means to study in vitro cell migration and proliferation. In such analysis, a cell monolayer that sits on a small electrode is electrically wounded and its spectral impedance is then continuously measured in order to monitor the healing process. The relatively slow dynamics of the cell healing have been extensively studied, while those of the much faster wounding phase have not yet been investigated. An analysis of the electrical properties of a particular cell type during this phase could give extra information about the changes in the cell membrane due to the application of the wounding current, and could also be useful to optimize the wounding regime for different cell types. The main issue when trying to register information about these dynamics is that the traditional measurement scheme employed in typical wound-healing assays doesn't allow the simultaneous application of the wounding signal and measurement of the system's impedance. In this paper, we overcome this limitation by implementing a measurement strategy consisting of cycles of fast alternating low- and high-voltage signals applied on electrodes covered with mammalian cells. This approach is capable of registering the fast impedance changes during the transient regime corresponding to the cell wounding process. Furthermore, these quasi-simultaneous high- and low-voltage measurements can be compared in order to obtain an empirical correlation between both quantities.Fil: Bellotti, Mariela. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Giana, Fabián Eduardo. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Bonetto, Fabian Jose. Comisión Nacional de Energía Atómica. Gerencia de Área de Energía Nuclear. Gerencia de Ingeniería Nuclear (CAB). Laboratorio Cavitación y Biotecnología; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentin