• 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 - 心臓組織の本来の環境に類似した生理学的条件下での収縮力測定を実現


FLEXcyte 96 は新次元の心筋細胞のin vitro収縮力測定を実現します。心筋細胞用に定義された弾力性のある基材を使用することで、成熟化および成熟化細胞の応答を促し、ハイスループットでの幹細胞由来心筋細胞の薬理評価系を可能にします。細胞は弾力性のある培養基材上に単層で接着し、同期拍動する単層細胞の収縮力が96ウェルプレートで測定されます。この独自技術により、心臓の機械的条件に近い生体を模した環境を実現しています。FLEXcyte 96は心毒性および安全性、高効率スクリーニングや基礎研究における構造的、機能的な収縮力測定のターンキーシステムです。


FLEXcyte 96 は CardioExcyte 96 の追加オプションです。FLEXcyte 96 ディスポ式プレートのポリジメチルシロキサン(PDMS)膜は、厚さが10μm以下で、高度な表面改質が施されており、ネイティブなヒト心筋組織の生理学的な伸縮性と強力な機械的支持を実現します。培養液の重さでたわんでいる間に、心筋細胞の律動的な収縮が96ウェルの膜を上に持ち上げます。このたわみの変化を測定することで、機械的応力を算出することができます。


システムは多様な市販の幹細胞由来心筋細胞(Ncardia,FUJIFILM Cellular Dynamics, Inc. (FCDI),Axol,NEXEL社など)でバリデートされています。ヒトiPS細胞由来心筋細胞(hiPSC- CMs)は陽性変力反応を示し、「成熟化」の為に追加でペーシング等による刺激は必要ありません。

僅かな細胞の応答も見逃しません。心筋細胞の収縮力測定により慢性および急性の両アプリケーションにおける安全性、有効性、毒性評価を確実に実施できます。FLEXcyte 96 は完全自動の測定装置であり、96ウェル同時測定が可能です。 

FLEXcyte 96 の主な特徴と優位性:

  • 真の収縮力測定
  • 成熟化細胞の応答取得を促進
  • 生理学的機械条件
  • ハイスループット,96ウェル同時測定
  • 急性および慢性評価
  • 光学ペーシングオプション

CardioExcyte 96/ FLEXcyte 96 パッケージには専用のインキュベーションシステムが含まれており、通常の培養インキュベータは不要です。システムを実験台に設置したままで温湿度およびCO2がコントロール可能です。
 CardioExcyte 96/ FLEXcyte 96 システムにはデータ解析とエクスポート用の強力なソフトウェアパッケージが同梱されており、効率性と簡便性を支える大きな特徴のひとつとなっています。

詳細情報:

オプション&特徴

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. It is suitable for various experimental conditions (e.g. hypoxia).


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.


ソフトウェア

 

CardioExcyte 96/ FLEXcyte 96 Software package

FLEXcyte 96 Analysis New

An adaptive signal detection algorithm extracts the positions and values of beating events. Besides beat intervals, amplitudes, rising and falling time, Pulse widths are detected. Furthermore, the area under the beat 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.

消耗品

 

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

Watch the video on FLX-96 Plate Handling


Icon CE   CardioExcyte 96 and   Icon FLEX   FLEXcyte 96 product flyer on plates available  logo pdf   (0.90 MB) 

データ&アプリケーション

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.

 

Digoxin Concentration response curves

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

Acute effects of digoxin on hiPSC cardiomyocytes (Cardiosight®-S). Overlay of mean beats at 60 min after application of several digoxin concentrations (1 nM – 10 µM). Bar graphs depict development of beating amplitude over 60 min for the same digoxin concentrations. Concentrations > 1 µM predominately promote cytotoxic effects.

 

 

 

Effect of Isoproterenol

FLEXcyte Isoproterenol data

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

 

Isoproterenol increases contraction force

FLEXcyte isoproterenol amplitude

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

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

 

Kinase inhibitor A-674563 – Arrhythmogenic effects on cardiomyocytes

FLEXCyte Arrhythmogenic Effect A 674563

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

Exemplary arrhythmia as observed 24 h after application of Kinase inhibitors A-674563. Aftercontractions (regular intervals and irregular intervals) were observed.

Kinase inhibitor Gefitinib – Arrhythmogenic effects on cardiomyocytes

FLEXCyte Arrhythmogenic Effect Gefitinib

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

Exemplary arrhythmia as observed 24 h after application of Kinase inhibitor Gefitinib. Aftercontractions (regular intervals and irregular intervals) and Fibrillations were observed, respectively.

Kinase inhibitor Nilotinib – Arrhythmogenic effects on cardiomyocytes

FLEXCyte Arrhythmogenic Effect Nilotinib

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

Exemplary arrhythmia as observed 24 h after application of Kinase inhibitor Nilotinib. Aftercontractions (regular intervals and irregular intervals) and beat rate variability were observed.

Kinase inhibitors – Chronic compound effects on cardiomyocytes

FLEXcyte kinase inhibitor Chronic effect

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

Here Structural and/or functional toxicity of Kinase inhibitors Trametinib, Sorafenib, Nilotinib and A-674563 was investigated. Compound incubation time was 5 days.

During investigations of chronic effects it could take days and weeks until onset of adverse effects. The CardioExcyte and FLEXcyte technology and the consumables are perfectly suited for such studies.

Positive Inotropes - Omecamtiv Mecarbil myosin complex activation

FLEXcyte Myosin Complex Activation Data front

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

Omecamtiv mecarbil increased both the contraction amplitude as well as the duration of the contraction-relaxation-cycle, indicating the positive inotropic effect based on activation of the myosin complex. The symmetry of the contraction-relaxation-cycle was not changed. 
Read the application note here.

 

ウェビナー&動画

2019 - FLEXcyte 96 Product Video

Icon FLEX   FLEXcyte 96 product video

A short introductory video of FLEXcyte

27.02.2021 | Presentation: Integration of mechanical conditioning into a high throughput contractility assay for cardiac safety assessment (In Japanese)

Icon FLEX FLEXcyte 96 Presentation

Date: February 27. 2021

210226 event image JSPS 2021

Speaker:
Mitsuyoshi Shimane (Nanion K.K Japan)

 

 

27.01.2021 | Webinar: Thinking outside the cardiac box

icon pl  Patchliner and Icon FLEX FLEXcyte 96 Webinar

Date: January 27. 2021

210127 webinar cardiac box

Speaker: 
Dr. Elena Dragicevic (Senior Sales and Alliance Manager; Nanion Technologies)

 

 

17.03.2020 | Webinar: A new technology to evaluate mature cardiac contractility on high throughput level

Icon FLEX   FLEXcyte 96,   Icon CE   CardioExcyte 96 Webinar

Date: March 17. 2020, 4:00 PM CET (11:00 AM EDT)

200207 blog image Webinar Announcement FLEXcyte

The Webinar focuses on the FLEXcyte 96 technology, an Add-on of the CardioExcyte 96 instrument. The analysis of cardiomyocyte contractility as well as data of short-termed and long-termed compound applications is discussed.  

Speakers:
Dr. Sonja Stölzle-Feix
Dr. Matthias Gossmann

インタビュー

innoVitro - Statement about FLEXcyte technology

Icon FLEX  “We have been working with Nanion for several years on technology development projects and joint commercialization. Nanion is a prime example of an agile approach and customer orientation.”

Dr. Matthias Gossmann
co-founder and CEO at innoVitro, Germany. (CRO, FLEXcyte Service Provider)

Icon FLEX  “Human iPSC-derived cardiomyocytes are the future of safe and efficient drug development. The FLEXcyte technology provides a tool for functional cardiac toxicology and efficacy screening on these cells. Force-frequency relation are the subject of current scientific discussions and require an assay technology that can accurately quantify them and we meet this need with the FLEXcyte 96.

Dr. Peter Linder
CTO innoVitro, Germany. (CRO, FLEXcyte Service Provider)

Merck - Statement about FLEXcyte technology

Icon FLEX  “We were very pleased with our choice to engage innoVitro’s contractility service. The studies using human iPSC-derived cardiomyocytes were tailored to our needs to provide results comparable to already existing (in house) data and the fast execution followed by a comprehensive study report completed the service perfectly.”

Nina Glaser
Head of Early Safety Electrophysiology, Merck Healthcare KGaA

NEXEL - Statement about FLEXcyte technology

Icon FLEX  “The FLEXcyte brings another dimension to iPS-derived cardiomyocyte based assays. Measuring contractility in such a direct and easy way allows us to understand the cell functionality better and will help us in both our product development and safety pharmacology research.

Choong-seong (Henry) Han DDS PhD
CEO and Founder at NEXEL Co., Ltd.

Northwestern University Feinberg School of Medicine - Statement about FLEXcyte technology

Icon FLEX  “We recently purchased the FLEXcyte-96 system through the NIH shared instrument grant (S10) program to be used by a diverse group of researchers who use cultured heart cells to study genetic and other cardiac disorders or who need to test lead compounds for cardiac toxicity. We have been thoroughly satisfied by the performance of the instrument and have been pleased with the great support from Nanion. The 96-well format enables critically important replication and the ability to conduct multiple simultaneous experiments. We are now exploring use of the instrument to interrogate other types of contractile cells. Given the enthusiasm from multiple investigators, we are going to purchase a second instrument..”

Alfred L. George, Jr.
Professor and Chair of Pharmacology, Northwestern University Feinberg School of Medicine

ダウンロード:

アプリケーションノート

製品カタログ

CardioExcyte 96 / FLEXcyte 96 Product Flyer - Plates

Icon CE   CardioExcyte 96 and   Icon FLEX   FLEXcyte 96 Product flyer  logo pdf   (1.3 MB)

FLEXcyte 96 - Product Sheet

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

論文

2020 - Integration of mechanical conditioning into a high throughput contractility assay for cardiac safety assessment

 Icon FLEX   FLEXcyte 96 Publication in the Journal of Pharmacological and Toxicological Methods (2020)

Authors:
Gossmann M., Linder P., Thomas U., Juhasz K., Lemme M., George M., Fertig N., Dragicevic E., Stoelzle-Feix S.

2019 - Higher throughput in vitro cardiac contractility recordings under physiological mechanical conditions

 Icon FLEX   FLEXcyte 96 white paper (2019)

Authors:
Stoelzle-Feix S., Juhasz K., Thomas U., Linder P., George M., Gossmann M.

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.

ポスター

プレゼンテーション

FLEXcyte 96 Brochure

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.