• FLEXcyte 96

    Cardiomyocytes cultivated on a flexible membrane
  • FLEXcyte 96

    Measure true cardiac contractility
  • FLEXcyte 96

    The complete setup fits on a lab benchtop
  • FLEXcyte 96

    Judge compound responses at a glance

FLEXcyte 96 - Contractility under physiological conditions

The FLEXcyte 96 brings in vitro contraction force measurements of cardiac cells to a new dimension. By using a well-defined, flexible substrate for cardiac cells, the system leverages maturity and mature responses of stem cell-derived cardiomyocytes to pharmacological compounds in a higher throughput format. In the 96-well plate, the cells adhere as monolayers on the flexible substrates and the contractility of the synchronized cell layers are recorded. This unique technology allows for recordings in a native-like environment close to mechanical conditions of the heart. The FLEXcyte 96 is a turn-key system for structural and functional contraction force recordings in cardiotoxicity, safety and efficacy screening and basic research.

The FLEXcyte 96 comes as an add-on for the CardioExcyte 96. With less than 10 μm in thickness and sophisticated surface modification, the polydimethylsiloxane (PDMS) membranes of the FLEXcyte 96 disposable plates offer physiological elasticity of native human heart tissue and strong mechanical support. While being deflected by the weight of the culture medium, rhythmic contraction of the cardiomyocytes lift the membranes in the 96-well upwards. By measuring the changes in deflection, the mechanical stress can be calculated.

The system has been validated with stem cell-derived cardiomyocytes from several providers (Ncardia, Cellular Dynamics International, Axol and NEXEL). Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC- CMs) display positive inotropic responses, no additional stimulation of “cell maturation” is necessary. Cardiac contraction force can also be measured on patient-derived cells.
No subtleties of cytotoxic responses are missed, measuring contractile forces on heart muscle cells for safety, efficacy and toxicity investigations in both chronic and acute time frames are performed reliably. The FLEXcyte 96 is a fully automated device, recording from 96 wells in parallel.

The benefits the FLEXcyte 96 offers include:

  • True contractility
  • Supports mature cell behavior
  • Physiological mechanical conditions
  • Higher throughput, 96-wells in parallel
  • Acute and chronic assessment of cell activity and toxicity
  • Optical pacing options

The CardioExcyte 96/ FLEXcyte 96 package includes an Incubation System which makes the system independent of an incubator. The system is placed on the bench top with maintained control over temperature, gas mix and humidity.
Efficiency and ease-of-use are facilitated by an outstanding software package for data handling and export - an essential part of the CardioExcyte 96/ FLEXcyte 96 system.

For detailed information:

Add-Ons and Features

CardioExcyte 96/ FLEXcyte 96 Platform

CardioExcyte Integra 1

The CardioExcyte 96/ FLEXcyte 96 package contains an Integra Viaflo Assist that provides automated multichannel pipetting for reproducible 96 well plate handling of cells and compounds.


FLEXcyte 96 Incubation System

FLEXcyte incubation system

The FLEXcyte 96 package includes an Incubation System. This means that the measurements are performed outside the cell culture incubator and the complete setup fits on a lab benchtop. The FLEXcyte 96 Incubation System controls temperature, gas mix and humidity.


FLEXcyte 96 SOL (Add-On)

Optical stimulation and investigation of contraction force in parallel:

CardioExcyte Sol 1

The stimulating optical lid, CardioExcyte 96/ FLEXcyte SOL, uses LEDs for spatially uniform stimulation of cells transfected with light-gated ion channels such as Channelrhodopsin2 (ChR2). After transfection of iPS cardiomyocytes with ChR2 the cells can be stimulated by blue light. Each light impulse induces a depolarization of the cells and thus an action potential is triggered. The advantages of optical stimulation over electrical stimulation include the highly precise timing, all cells of the beating network are stimulated exactly at the time of the light stimulus. In contrast, electrical stimulation propagates from the electrode across the well and thus cells are stimulated progressively. A mean beat calculation of precisely timed beats enables in-depth compound analysis and concentration response dependencies to be obtained. This is one of the key software capabilities of the CardioExcyte Control/ DataControl software package that is provided with each CardioExcyte 96/ FLEXcyte 96 system.


Software

 

CardioExcyte 96/ FLEXcyte 96 Software package

FLEXcyte 96 Analysis

An adaptive signal detection algorithm extracts the positions and values of beating events. Besides beat intervals, amplitudes, rising and falling time, Pulse witdhs are detected (upper figure). Furthermore, integrals (blue and red) and arrhythmia (yellow) are identified and quantified as well.

The CardioExcyte/ FLEXcyte Control software supports online analysis of contractility parameters. The unique Mean Beat Function automatically visualizes the average of beat traces from one well, enveloped by the standard deviation, indicating the consistency of the beat pattern within the recorded well, i.e. if the cellular network is synchronously beating or not. The control software is intuitive and easy-to-use, at the same time very powerful in terms of experimental setup and online visualization of the recorded data.

The DataControl 96 software package is an independent software package to load and analyze data recorded on the CardioExcyte 96 or FLEXcyte 96. The analysis template can be saved and reloaded. Customized export formats of analysis results are integrated.

Consumables

 

FLX-96

FLEXcyte plate principle

The FLX-96 FLEXcyte membrane plates come in a standard 96-well format, allowing for automated liquid handling and easy integration into your lab procedures. After 7 days of culture, the cells have formed a biohybrid material with the membranes and are ready for assay. For further maturation in the physiological environment provided by the FLEXcyte 96 plates, the cells can be cultured for up to 4 weeks. The FLX-96 plates are a proprietary innovative product by innoVitro, developed for the FLEXcyte 96. It is produced and quality-assured in-house at innoVitro headquarters and shipped to our international customers.
With less than 10 μm in thickness and sophisticated surface modification, the polydimethylsiloxane (PDMS) membranes of the FLEXcyte 96 plates combine both physiological elasticity of native human heart tissue and strong mechanical support.


Description and Material

• Standard 96-well plate format
• Working volume: 200 µl (surface 34 mm2)
• Substrate: <10 µM thick PDMS (polydimethylsiloxane) flexible membrane
• Supports mature cell behavior


Available plate type:

"FLX-96, FLEXcyte 96 Membrane Plates - standard": Type standard

Data and Applications

Cardiac Action Potentials - Digoxin Concentration response curves

FLEXcyte Digoxin

Icon FLEX   FLEXcyte 96 data and applications:
Cells were kindly provided by NEXEL.

Digoxin concentration response curves, mean IC50 calculation (n=40). A reduction of beating amplitude in a concentration dependent manner can be observed, concentrations > 1 µM predominately promote cytotoxic effects.

 

Cardiac Action Potentials - Effect of Isoproterenol

FLEXcyte Isoproterenol data

Icon FLEX   FLEXcyte 96 data and applications:
Cells were kindly provided by Cellular Dynamics.

Isoproterenol is enhancing contractile force. Upon application of increasing Isoproterenol concentrations a beating frequency increase is observed, along with an increased beating amplitude (positive force-frequency relationship).

 

Cardiac Action Potentials - Detection of cardiac arrhythmia

FLEXcyte Arrhythmia data

Icon FLEX   FLEXcyte 96 data and applications:
Cells were kindly provided by NEXEL.

Contractile behavior of NEXEL cells. DataControl software allows an overview on mean beats including standard deviations from all 96-wells. Thus, arrhythmia or rhythmic beating can be judged at a glance.

 

Cardiac Action Potentials - Isoproterenol increases contraction force

FLEXcyte isoproterenol amplitude

Icon FLEX   FLEXcyte 96 data and applications:
Cells were kindly provided by Cellular Dynamics.

Amplitude increase of contraction signals as % of control plotted against increasing Isoproterenol concentrations.

 

Webinars and Movies

2019 - FLEXcyte 96 Product Video

Icon FLEX   FLEXcyte 96 product video

Short introduction

Downloads:

Product Sheets

FLEXcyte 96 - Product Sheet

Icon FLEX   FLEXcyte 96 product sheet   logo pdf   (0.5 MB)

Publications

2016 - Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

 Icon FLEX   FLEXcyte 96 alike technology publication in Cellular Physiology and Biochemistry (2016)

Authors:
Goßmann M., Frotscher R., Linder P., Neumann S., Bayer R., Epple M, Staat M., Artmann A., Artmann G.M.

Posters

Presentations

 

 

 

 

 

 

 

 

 

 

 

 

FLEXcyte 96 Brochure

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