
Preclinical Studies. For users of cell impedance sensing, multielectrode array and the voltagesensing optical platforms (ACEA xCELLigence, Nanion Cardioexcyte'96, Axion Maestro, Molecular Devices FLIPR, Hamamatsu FDSS, etc.), CYBERnano has developed a SaaS platform: easyBEAT to facilitate the analysis of your impedance, field potential and fluorescence signals with the aim to speed up your analysis and better control statistical reliability of your results.

Clinical Studies. For 12 channels ECG and Hölter ECG signals, CYBERnano has developed new computational tools for the automatic delineation and full morphologic analysis of short and long ECG signals in ICH E14 studies.
easyBEAT IMP : characterization of effects on viability & contractility
iCardio IMP is a computational service devoted to cardiomyocyte impedance assays. This service allows you to quickly compute, compare and rank contractility effects of your compounds. 5 timecharacteristics (FASTI): Frequency (Beating Rate), Amplitude, Beating Shape, Viability Trends and Beating Irregularity are firstly determined.

Frequency: providing an estimate of the mean beating rate (bpm) in each sweep;
 Amplitude: estimating the average peaktopeak magnitude in each sweep;

Shape: quantitatively characterizing the mean beating pattern in each sweep;

Trends of Viability : informing about the compound effect on the cardiomyocyte viability (cell index trend) ;

Irregularity: indicating how much the beat pattern is changing within each sweep*;
*sweep : period of beating recording, its duration generally varies between 20 and 60s.

xCELLigence Cardio (ACEA Biosciences)

CardioExcyte 96 (Nanion)
Technology Compatibility
Fig.A : Overview of FASTI indices over time from cardiomyocytes exposed to Sunitinib (cardiotoxic compound). Cardiomyocytes were exposed to three concentrations of Sunitinib (positive control compound): 100nM (light red), 1muM (medium red), 10muM (dark red) for 24h. Compound addition occurred at t=53.5h as indicated by the black vertical line. Nine wells (triplicate condition for each concentration) of culture are examined. We clearly observe instability of amplitude, frequency and shape, acceleration of irregularities, and a drop of cardiomyocyte viability a few hours after Sunitinib administration.
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Fig.B : Overview of FASTI indices over time from cardiomyocytes exposed to Famotidine (noncardiotoxic compound). Cardiomyocytes were exposed to three concentrations of Famotidine: 100nM (light blue), 1muM (medium blue), 10 muM (dark blue) for 24h. Compound addition occurred at t=49h as indicated by the black vertical line. The different grade of blue are not always easy to observe due to the curve overlapping. Nine wells (triplicate condition for each concentration) of culture are examined. Except for some rare events due to technical artefacts, the FASTI indices are stable, no significant change and no irregularity are detected in the 24h timeframe.
2 summary statistics of the FASTI indices are computed over all the experimental time range and are used to test dose response relationship (Figures below). Those two additional attributes provide clarifications about the threshold concentration effects of each molecule. The Student's ttest is used to detect the statistical significance of each concentration effect with respect to a given control. A global score is finally proposed to compare the alteration effects of the tested pharmaceutical agents on the cardiomyocyte contractility. To this aim, we have proposed a new cardioeffect scale graduated from 0 (no influence) to 10 (critical effect). A median concentration EC50 parameter is estimated to rank the compounds.
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Summary of concentrationeffects induced by Doxorubicine on mouse cardiomyocytes with four levels of concentration: 100nM; 1muM; 10muM and 100muM. Fig.A : FASTI indices: blue dots correspond to control values, green dots indicate no significant change w.r.t. control and red dots point out significant changes compared to control data. Each time red dots are detected, the global effect score is increased by one unit. Fig.B : Global effect scores. Minimum score (0) means that the FASTI parameters are not significantly different compared to control data (cardiomyocytes exposed to 0.1% DMSO). A score of 10 corresponds to severe effects often manifested by a beating arrest of the cardiomyocytes. Highest score for Doxorubicine is 8. Fig.C : Estimated EC50 value: 9.7muM for Doxorubicine.
References

L. Batista, T. Bastogne, A. Delaunois, J.P. Valentin, and F. Atienzar, A statistical signal processing method to rank drug effects in cardiomyocyte impedance assays, submitted to Biomedical Signal Processing and Control, 2018.

L. Batista, T. Bastogne, F. Atienzar, A. Delaunois, and J.P. Valentin, A datadriven modeling method to analyze cardiomyocyte impedance data, Proc. of the SPS Annual Meeting, (Berlin, Germany), September 2427 2017.
easyBEAT MEA : characterization of electrical activity
iCardio MEA is a computational service devoted to the analysis of field potential signal. This service allows you to quickly compute, compare and rank electrophysiological effects of your compounds. 4 timecharacteristics (FASI): Frequency (Beating Rate), Amplitude, Beating Shape and Beating Irregularity are firstly determined.

Frequency: providing an estimate of the mean beating rate (bpm) in each sweep;
 Amplitude: estimating the average peaktopeak magnitude in each sweep;

Shape: quantitatively characterizing the mean beating pattern in each sweep;

Irregularity: indicating how much the beat pattern is changing within each sweep*;
*sweep : period of beating recording, its duration generally varies between 20 and 60s.

xCELLigence Cardio ECR (ACEA)

Maestro (AXION Biosystems)

CardioExcyte 96 (Nanion)
Technology Compatibility
2 summary statistics of the FASTI indices are computed over all the experimental time range and are used to test dose response relationship. Those two additional attributes provide clarifications about the threshold concentration effects of each molecule. The Student's ttest is used to detect the statistical significance of each concentration effect with respect to a given control. A global score is finally proposed to compare the alteration effects of the tested pharmaceutical agents on the cardiomyocyte contractility. To this aim, we have proposed a new cardioeffect scale graduated from 0 (no influence) to 10 (critical effect). A median concentration EC50 parameter is estimated to rank the compounds.
References

L. Bastista, L. Doerr, M. Beckler, N. Fertig, and T. Bastogne, Coupled impedance & field potential data analysis of in vitro cardiomyocyte assays. Proc of the SPS Annual Meeting, (Berlin, Germany), September 2427 2017.
iCardio FPD is a new computational service devoted to the robust estimation of FPD from multielectrode arrays. Instead to compute FPD separately for all electrodes we have developed a global estimation for a higher accuracy.
easyBEAT FPD : robust estimation of the field potential duration

Maestro (Axion BioSystems)
Technology Compatibility
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Fig.A : Raw MEA signal. Fig.B : Delineation of the beating waves. Fig.C : "T" waves extracted from all electrodes after signal processing. Fig.D : Global estimation of the "T" wave and Field Potential Duration.
easyBEAT FLIPR : automatic detection of EAD events
iCardio FLIPR is the last computational service developed by Cybernano to detect EAD events from FLIPR signals. In addition to FPD, 9 other parameters are estimated for each beating wave:

Beat Rate

Amplitude

CTD 90% and 30%

RR & Max(RR)

FR & Max(FR)

Time to Next Beat

FLIPR Tetra (Molecular Devices)

FDSS/μCELL (Hamamatsu)
Technology Compatibility
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Fig.A : Map of plate after data analysis: green wells (no EAD event), orange (moderate risk of EAD), red (serious risk of EAD). Fig.B : Ca2+ fluorescence signal for one selected well. Fig.C : Table of estimated parameters for each beating wave.
References

L. Guo, M. Furniss, J. Hamre, L. Batista, T. Bastogne, Z. Yan, J. Wu, S. Eldridge, and M. Davis, Assessing functional and structural cardiotoxicity in cultured human iPSCcardiomyocytes. Proc of the SPS Annual Meeting, (Berlin, Germany), September 2427 2017.
easyBEAT ECG : automatic delineation of ECG signals
iCardio ECG is a computation service specifically designed to perform automatic delineation of ECG and ECG Hölter signals and to estimate:

Mean heart Rate ;

PR interval ;

QRS duration ;

QT interval ;

QTcB & QTcF intervals ;

RR interval.

P. Guyot, P. Voiriot, E. Djermoune, S. Papelier, C. Lessard, M. Felices, and T. Bastogne, “Rpeak detection in holter ecg signals using nonnegative matrix factorization,” in submitted to Computing in Cardiology conference, 2018.

P. Guyot, P. Voiriot, S. Papelier, L. Batista, and T. Bastogne, “A comparison of methods for delineation of wave boundaries in 12 Lead ECG,” in Proc of the SPS Annual Meeting, (Berlin, Germany), September 2427 2017.