• ナニオンのCiPA製品ラインナップ

    Patchliner & SyncroPatch 384PE (CiPA ion channel working group); CardioExcyte 96 (CiPA myocyte working group)

  • CiPA hERGプロトコール

    This protocol was used for hERG studies on the Patchliner and SyncroPatch 384PE.

  • HTS CiPA hERGアッセイ

    Effects of Cisapride using the CiPA hERG protocol on the SyncroPatch 384PE

  • 心筋 & イオンチャネルデータのブリッジ

    Arrhythmic Field potentials in iPSC-derived Cardiomyocytes (CardioExcyte 96) and hERG current inhibition (SyncroPatch 384PE)

  • ギガシール HTSパッチクランプ

    CiPA-specified cardiac ion channels recorded at high throughput

  • ギガシール HTSパッチクランプ

    High throughput recordings of cardiac ion channels at physiological temperature

  • CardioExcyte 96 スクリーニングプラットフォーム

    CardioExcyte 96 with integrated liquid handling for cardiac safety screening

CiPA - Comprehensive in vitro Proarrhythmia Assay

The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative aims to replace the preclinical hERG current assay required under the ICH S7B safety pharmacology guidelines and clinical TQT study, which provides a surrogate marker of Proarrhythmia, with more translationally relevant assessments of proarrhythmic risk (Sager et al., 2014). CiPA intend to achieve this by evaluating proarrhythmic risk of evolving drug candidates based on an understanding of the electrophysiologic mechanisms responsible for proarrhythmia linked to Torsades de pointes (TdP) and QT prolongation.


The CiPA workstreams

CiPA Work Groups

The Comprehensive in Vitro Proarrhythmia Assay (CiPA) paradigm was initiated in 2013. The Steering Team is comprised of partners from the US FDA, HESI, CSRC, SPS, Japan NIHS, PMDA, EMA and Health Canada. A number of participating organizations, amongst them Nanion Technologies, build the backbone of the initiative. The CiPA work streams include: In Silico, Myocyte, Ion Channel, and Clinical Translation working groups. 

Nanion is a committee member of the Ion Channel HTS Team and a participant in the Myocyte Working Group. Nanion has a long-standing interest and extensive experience in automated patch clamp screening of cardiac ion channels. Label-free contractility and extracellular field potential recordings of stem cell-derived cardiomyocytes (iPSC-CMs) is also available in our portfolio. Our instruments are used for safety screening by major pharmaceutical companies and CROs worldwide and we are happy to assist you in setting up your CiPA assays.


Results of Phase I Studies

CiPA Table Phase I smallThe Ion Channel Work Group finalized its phase I study in 2017. Besides further external sites, Nanion Technologies in Germany, USA and Japan participated with the Patchliner and the SyncroPatch 384PE in this study. 

The image on the left hand side displays the results of the blocking effect of 12 compounds on hERG. 
The results are in good agreement with manual patch clamp data (Crumb et al., 2016).  

 


Nanion's products in CiPA workstreams


icon sp96   SyncroPatch 384/768PE - Patch clamp meets HTS 

Nanion CiPA IconThe SyncroPatch 384PE (upgradeable to 768PE) is a high throughput patch clamp instrument recording from up to 384 (or 768) cells simultaneously. The SyncroPatch 384/768PE is the highest throughput patch clamp instrument on the market with giga-seal data quality. 
The SyncroPatch 384PE is used for CiPA ion channel working group studies.
Request the CiPA assay protocol for the SyncroPatch 384PE here.

icon pl   Patchliner - Versatile and sophisticated

Nanion CiPA IconThe Patchliner is a fully automated planar patch clamp instrument recording from up to 8 cells simultaneously. With its vast experimental freedom and gigaseal data quality, the Patchliner is one of the most versatile patch clamp instruments on the market.
The Patchliner is used for CiPA ion channel working group studies.
Request the CiPA assay protocol for the Patchliner here

Icon CE   CardioExcyte 96 - Combined contractility, electrophysiology and cell viability

Nanion CiPA IconThe CardioExcyte 96 is a hybrid system recording both contractility and electrophysiology of intact cardiomyocyte networks. In addition, the base impedance is continuously and automatically monitored as a measure of acute and chronic cell activity. No subtleties of cytotoxic responses are missed, this includes non-contractile cell types such as hepatocyte-like cells or cancer cells as well as contractile cardiac cells. Impedance and extracellular field potential measurements are performed at high resolution, are non-invasive and label-free. The CardioExcyte 96 is a fully automated device, recording from 96 wells at a time. 
The CardioExcyte 96 is used for CiPA myocyte working group studies.
Request the CiPA assay protocol for the CardioExcyte 96 here.

Ion Channel Work Group (ICWG)

ICWG: Description and History

"Ion Channel Working Group (ICWG)は,Safety Pharmacology Society (SPS)により2013年12月に設立されました。当初の役割は,In Silico Working Group (ISWG)との密な連携を取り,adult human ventricular myocyteのコンピュータモデルの開発におけるイオンチャネル部分の情報提供を行い,薬物誘発性TdPの臨床リスク予測においてCiPA イニシアチブで使用することでした。"

"The original remit of the ICWG was: 1) CiPA評価における主要なイオンチャネルの選定; 2) データ取得に必要な堅牢かつ信頼性,再現性のある電位固定プロトコールの開発し,in silico modelのバリデーションを可能にする; 3) モデルの予測性を最適化するために,チャネルのどの生物物理学的,薬理学的特性について薬物の影響を評価するかを明確にする (例えば,阻害活性 (IC50), 阻害のキネティクス, rate/use/voltage dependence); 4) to define the requirements needed to transition the various ion channel protocols from manual to automated high throughput (HT) patch clamp platforms, in order to adapt to the screening environment present in most pharmaceutical companies."

Selected recombinant human channels: "IKr (hERG), ICa (L-type; Cav1.2), INa (Nav1.5 peak and late current); ITO (Kv4.3); IKs (KCNQ1 + KCNE1), and IK1 (Kir2.1). Following the selection, the ICWG set out to design standardized voltage clamp protocols for each of these channels."

(Source: Journal of Pharmacological and Toxicological Methods "The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative — Update on progress. Colatzky et al. (2016) ")


Progress of the Ion Channel Work Group

"Protocols were developed and manual experimental work was completed. The High-Throughput Systems (HTS) studies to evaluate and characterize the automated patch clamp systems is underway. The training compounds have been completed for both manual and automated systems and data analysis initiated. The second phase of the HTS study with the validation compounds is underway. Additional ion channel studies will likely be planned beyond 2017 to further validate the model."

CiPA Ion Channel Workstream

(Source: CiPAproject webpage April 2018 "CiPA Workstream Timelines")


Data, Applications and Publications on the six Cardiac Ion Channels investigated by the "CiPA Ion Channel Work Group"

Myocyte Work Group (MWG)

MWG: Description and History

The role of human cardiac stem cell derived cardiomyocytes (hSC-CMs) within the CiPA paradigm is to confirm in silico reconstructions of the electrophysiologic effects of drugs. This will be accomplished by evaluating the acute effects of drugs on the electrical activity of hSC-CM's using higher throughput approaches that enable more comprehensive and robust assessments earlier in the drug discovery process. Typical techniques involved include assessing changes in the extracellular field potentials of spontaneously active hSC-CMs using multielectrode array (MEA) platforms, or changes in the action potential configuration recorded optically using voltage-sensing dyes (VSD)."

"A pilot study was conducted by the Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee Myocyte Subteam to evaluate reproducibility and variability of electrophysiologic responses across cells, platforms and volunteer study sites for 8 compounds, Mexiletine, Nifedipine, E-4031, JNJ-303, Flecanide, Moxifloxacin, Quinidine and Ranolazine. Overall, most sites detected changes in repolarization consistent with clinical findings, with the greatest source of variability attributed to study site."

"More recently, the HESI Myocyte Subteam was awarded a Broad Area Announcement Grant from the FDA to extend the pilot study to a larger set of 28 compounds categorized according to high, intermediate, and low/no risk of proarrhythmia based on clinical findings. The effects of these CiPA reference standards will be evaluated by a core group in this Phase II Validation study across four MEA and two VSO technology platforms using two commercially viable hSC-CM preparations." Results will be compared with prospective in silico reconstructions (based on voltage clamp studies) and published studies employing hSC-CMs from non-core laboratories and consortia for the same 28 compounds."

(Source: Journal of Pharmacological and Toxicological Methods "The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative — Update on progress. Colatzky et al. (2016) ")


Progress of the Myocyte Work Group

"The publication detailing the results of the Pilot Study is now available online. The Phase II Validation Study has been completed and the publication detailing the results has been submitted."

CiPA Myocyte Workstream 2

(Source: CiPAproject webpage May 2018 "CiPA Workstream Timelines")


Nanion for CiPA:

データ & アプリケーション

NaV1.5 - Late Current Analysis using the CiPA Protocol

CiPA PE NaV1 5 Pharmacology late currenticon sp96   SyncroPatch 384/768 PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing NaV1.5 current traces in response to the CiPA voltage step protocol, measured on the SyncroPatch 384PE using whole cell patch clamp methodology and single-hole chips. The NaV1.5 late current was activated by the application of 60 nM ATX-II. The IC50 value of Ranolazine of the late Sodium current current was determined as 40.4 µM.

 

hERG - Pharmacology at Physiological Temperature using the CiPA Protocol

CiPA PE hERG Pharmacology 35DegreeCelsiumicon sp96   SyncroPatch 384/768 PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol at 35 degree Celsius. Measured on the SyncroPatch 384PE using perforated patch clamp methodology (Escin) and multi-hole chips (4 holes per well). The IC50 value of Erythromycin of the peak current was determined as 60.5 µM. 

 

KV4.3 - Pharmacology of Metropolol Tartrate, using the CiPA Protocol

CiPA PE KV4.3 2icon sp96   SyncroPatch 384/768 PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV4.3 current traces in response to the CiPA voltage step protocol, measured on the SyncroPatch 384PE using the whole cell patch methodology and single-hole chips. The IC50 value of Metropolol Tartrate was determined as 128 µM.

 

 

CaV1.2 - Pharmacology of Nifedipine, using the CiPA protocol

icon sp96   CiPA PE CaV1 2 2SyncroPatch 384PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hCaV1.2/β2/α2δ1 current traces in response to the CiPA voltage step protocol and the corresponing current-voltage relationship plot. Measured on the SyncroPatch 384PE using perforated patch methodology (Escin) and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was 94%. The IC50 value of Nifedipine was determined as 106 nM.

 

hERG - Pharmacology of Cisapride, using the CiPA protocol

icon pl   CiPA PL hERG CisapridePatchliner data and applications:
Cells were kindly provided by Charles River.

The effect of cisapride on hERG currents was investigated, using the CiPA voltage step protocol. Measured on the Patchliner the perforated patch methodology (Escin) and multi-hole chips (4 holes per well) were used. The IC50 value of Cisapride was determined as 112 nM.

hERG - Pharmacology using the CiPA Protocol

CiPA PE hERG Pharmacologyicon sp96   SyncroPatch 384/768 PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol. Measured on the SyncroPatch 384PE using whole cell patch clamp methodology and multi-hole chips (4 holes per well). The IC50 value of the following compounds of the peak current was determined as 4.18 µM for Diltiazem, 37.4 nM for Terfenadine, 971 nM for Quinidine, 63 µM for Mexiletine, 431 nM for Verapamil and 4.54 µM for Ranolazine. 

hERG - recordings with great stability using the CiPA step ramp protocol

CiPA PE hERG Pharmacology Stabilityicon sp96   SyncroPatch 384PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol. Measured on the SyncroPatch 384PE using perforated patch clamp methodology (Escin) and multi-hole chips (4 holes per well). 

Cardiac Ion Channels - Pharmacology of Sotalol

CiPA PE CE Pharmacology SotalolIcon CE    CardioExcyte 96 and   icon sp96   SyncroPatch 384PE data and applications:
Cells were kindly provided by Charles River and Cellular Dynamics.

The image on the left hand side displays the results of the blocking effect of Sotalol on hERG. The result is in good agreement with manual patch clamp data (Crumb et al., 2016). The compound induced arrhythmia when iPSC-CM were exposed to a minimum concentration of 10 µM. Arrhytmic events were both detected in field potential recordings as well as in the impedance based contractility measurements.

Cardiac Ion Channels - Pharmacology of Vandetanib

CiPA PE CE Pharmacology VandetanibIcon CE    CardioExcyte 96 and   icon pl   Patchliner data and applications:
Cells were kindly provided by Charles River and Cellular Dynamics.

The image on the left hand side displays the results of the blocking effect of Vandetanib on hERG, NaV1.5, CaV1.2 and KV4.3. The compound induced arrhythmia when iPSC-CM were exposed to a minimum concentration of 1 µM. Arrhytmic events were both detected in field potential recordings as well as in the impedance based contractility.

KV4.3 - Pharmacology of Quinidine

CiPA PE Kv4 3icon sp96   SyncroPatch 384/768 PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV4.3 current traces in response to the CiPA voltage step protocol. Measured on the SyncroPatch 384PE using the whole cell patch methodology and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was  95.3%. The IC50 value of Quinidine was determined as 21.2 µM (Literature: 79.3 µM, Crumb et al., J Pharmacol Toxicol Methods. 2016).

Kir2.1 - Pharmacology of Barium

CiPA PE Kir2 1icon sp96   SyncroPatch 384/768 PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing Kir2.1 current traces in response to a voltage step protocol. Measured on the SyncroPatch 384PE using the whole cell patch methodology and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was  93%. The IC50 value of Barium was determined as 6.38 µM (Literature: 16.2 µM, Schram et al. Cardiovasc Res. 2003).

hERG - Application of "Sticky Compounds"

application16 herg 2

icon pl   Patchliner data and applications:
hERG expressing HEK293 cells were kindly provided by Cytomyx/Millipore.

Even sticky compounds pose no problem for the Patchliner. IC50 measurements of well known sticky substances were determined on the Patchliner: Terfenadine IC50 = 11.0 ± 3 nM, Flunarizine IC50 163.7 ± 19 nM and Cisapride IC50 8.9 ± 3 nM.

NaV1.5 - Stable Access Resistance

p35 2 VoltContricon pl   Patchliner data and applications: 
Cells were kindly provided by Millipore.

The I/V-characteristics of NaV1.5 currents (HEK293) are shown together with the repeated dose dependent block by TTX (lower panel). Five concentrations of TTX (0.3, 1, 3, 10, 30 μM) were applied, followed by washout with antagonist-free buffer and re-application of the same TTX concentrations. 

hERG - Efficient Screening

p34 2 hERG II Sum

icon pl   Patchliner data and applications:
Cells were kindly provided by Cytomyx/Millipore.

The effects of six different blockers (terfenadine, cisapride, E4031, astemizole, propafenone, quinidine) on hERG currents (HEK293 cells) were investigated. Expected IC50 values for the different compounds were obtained. In two days, 119 full dose response curves were collected by a single person. Data was analyzed using Nanion’s Data Analysis Package, a very efficient and convenient data analysis tool!

hERG - Simple Data Analysis

hERG Screenshot Data Analysis Tool 1 700

icon pl   Patchliner data and applications:

With our analysis tools, especially programmed routines in Igor make dose response curves, raw data and current time courses easily accessible. Also, creating average dose response curves over multiple experiments - even conducted on different days - remains easy.

hERG - Block at Physiological Temperature

AppNote hERG TEmp

icon pl   Patchliner data and applications:
Cells were kindly provided by Cytomyx/Millipore, UK.

The effects of erythromycin on hERG currents were tested at different temperatures. Erythromycin has been shown to block hERG channels at physiological temperature with an IC50 of approx. 40 µM. However, at RT erythromycin is much less potent. For more details on these experiments please refer to the Application Note

 

hERG - Stable Recordings with Accurate Pharmacology

Syncro hERG 2icon sp96   SyncroPatch 384PE data and applications: 
Cells were kindly provided by Charles River Laboratories.

Current-voltage relationship of hERG (Kv11.1) expressed in HEK293 is shown along with pharmacology of 4 hERG-active compounds. The current-voltage relationships for all 384 wells (top) using perforated patch (Escin) and multi-hole chips (4 holes per well) are shown. In all 384 wells, a hERG-mediated current was observed with peak amplitude >700 pA at -20 mV. Using a pharmacology voltage protocol, experiments were stable lasting over 20 minutes. Concentration response curves for astemizole, pimozide, cisapride and terfenadine revealed IC50 values consistent with those found in the literature. 

hERG - Stable Recordings

application16 herg 1 small

icon pl   Patchliner data and applications:
Cells were kindly provided by Cytomyx/Millipore, UK.

A series of drug concentrations can be applied to each cell. The top figures show the original traces and the corresponding average dose-response curve. Five concentrations of Quinidine (0.1, 0.3, 1, 3 and 10 μM) have been applied.

The lower figure shows the corresponding Imax (-40 mV) including a wash out step and an additional application of the blocker to demonstrate the stability of whole cell recordings.

 

NaV1.5 - Lidocaine Block

application hnav15 3 small

icon pl   Patchliner data and applications:
Cells were kindly provided by Cytomyx/Millipore.

Full dose response curves at different holding potentials were recorded for each cell (hNav1.5 in HEK293). Currents were elicited by a 10 ms voltage step to 0 mV. Plotted are average peak currents as a function of holding potential and lidocaine concentration. 

hERG - Pharmacology of Sotalol, Terfenadine, Verapamil (Results CiPA Phase I Study)

icon pl   CiPA PL phase 1 results 3Patchliner data and applications:
Cells were kindly provided by Charles River.

The effect of four compounds on hERG currents were investigated, using the CiPA voltage step protocol. Measured on the Patchliner the perforated patch methodology (Escin) and multi-hole chips (4 holes per well) were used. The IC50 value of Sotalol was determined as 157 µM, Terfenadine as 82.8 nM and Verapamil as 485 nM.

hERG - Pharmacology of Mexiletine, Quinidine, Ondansetron, Ranolazine (Results CiPA Phase I Study)

icon pl   CiPA PL phase 1 results 2Patchliner data and applications:
Cells were kindly provided by Charles River.

The effect of four compounds on hERG currents were investigated, using the CiPA voltage step protocol. Measured on the Patchliner the perforated patch methodology (Escin) and multi-hole chips (4 holes per well) were used. The IC50 value of Mexiletine was determined as 77.3 µM, Quinidine as 1.04 µM, Ondansetron as 1.13 µM and Ranolazine as 11.9 µM.

hERG - Pharmacology of Bepridil, Dofetilide, Cisapride, Diltiazem (Results CiPA Phase I Study)

icon pl   CiPA PL phase 1 results 1Patchliner data and applications:
Cells were kindly provided by Charles River.

The effect of four compounds on hERG currents were investigated, using the CiPA voltage step protocol. Measured on the Patchliner the perforated patch methodology (Escin) and multi-hole chips (4 holes per well) were used. The IC50 value of Cisapride was determined as 112 nM, Bepridil as 178 nM, Dofetilide as 33.9 nM and Diltiazem as 14.5 µM.

Cardiomyocytes - Myocyte phase II study: CiPA conform analysis and arrhythmia detection

Icon CE   CardioExcyte CiPAII 1CardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

Nanion developed a CiPA conform analysis for the Myocyte phase II study. The feature comes along is included in our CiPA analysis routine. Automated arrhythmia detection is just one highlight out of many when it comes to the CardioExcyte 96 software.

Cardiomyocytes - Effects of verapamil on impedance (left) and EFP (right) signals of Cellartis Cardiomyocytes

Icon CE   CardioExcyte VerapamilCardioExcyte data and applications:
Cells were kindly provided by Takara Bio Cellartis Clontech.

(A) Impedance (left) and EFP signals (right) in control conditions
(B) Upon application of 10 nM verapamil
(C) Upon application of 100 nM verapamil.
(D) The mean beats for impedance (left) and EFP (right) are shown in D

 

 

 

 

Cardiomyocytes - Effects of sotalol on impedance (left) and EFP (right) signals of Cellartis Cardiomyocytes

Icon CE   CardioExcyte SotalolCardioExcyte data and applications:
Cells were kindly provided by Takara Bio Cellartis Clontech.

Impedance (left) and EFP signals (right) in control conditions (A) and 1 μM sotalol (B) are shown. 
Irregular beating can be observed in the presence of sotalol.

Cardiomyocytes - Effect of E4031 on the impedance and EFP signals on iCell cardiomyocytes

Icon CE   CardioExcyte E3031CardioExcyte data and applications:
Cells were kindly provided by Cellular Dynamics.

Effect of the specific hERG blocker, E4031, on the impedance and EFP signals. A Impedance signal of 12 wells in control conditions (left) and the same 12 wells after 13 mins incubation in E4031 at the concentrations indicated (right). E4031 (300 nM, 3 mins incubation) induces EAD, shown in the inset, which can lead to potentially fatal ventricular arrhythmias. B EFP signal of 12 wells in control conditions (left) and the same 12 wells after 13 mins incubation in E4031 at the concentrations indicated (right). E4031(300 nM, 30 mins incubation) also causes arrhythmic effects in the EFP mode shown in the inset.

Cardiomyocytes - Nifedipine and its concentration dependent effect on Cor.4U cells

Icon CE   Nifedipine Cor4UCardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

Nifedpinie is a dihydropyridine calcium channel blocker that primarily blocks L-type calcium channels. Impedance and EFP recordings on Cor.4U cells reveal a concentration dependent effect on impedance amplitude, beat rate and also a shortening of the FPD as expected.

Cardiomyocytes - Tetracaine dose response curves as recorded with Cor.4U cells

Icon CE   Tetracaine Cor4UCardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

Impedance amplitude is not changed by addition of increasing concentrations of Tetracaine (left panel), while beat rate of Cor.4U® cells is decreasing. For example, 29.6µM of Tetracaine decreased the beat rate by ~60% when compared to pre-addition values. Cumulative dose-response relationships indicate Tetracaine potency for same-well additions. Representative raw traces for impedance signals (middle panel) clearly indicate a decrease in cell monolayer beat rate with increasing concentrations of Tetracaine.
Extracellular Field Potential (EFP) spike amplitude is decreased by cumulative Tetracaine dose applications to the same monolayer of Cor.4U® hIPSC-CMs (top right), in agreement with compound mechanism of action. Representative raw traces for EFP signals (bottom graph) clearly indicate a decrease in spike amplitude.

Cardiomyocytes - Data from different cell providers

Icon CE   CardioExcyte different ProvidersCardioExcyte data and applications:
Cells were kindly provided by Axiogenesis, Cellular Dynamics, GE Healthcare, Pluriomics, ReproCell, Takara Bio Cellartis Clonetech.

The CardioExcyte 96 allows for
• Non-invasive, label-free measurements of beating cardiomyocyte networks
• 96 recording wells in parallel with 1 ms time resolution
• Quick experiments or long-term compound effects on cardiotoxicity
• Real-time access to beating parameters
• Outstanding software for data analysis and export
• Cost effcient consumables - 96-well format

KV7.1 (KVLQT) - Dose-response curve

icon sp96   170922 KV7.1 Data SyncroPatch384PESyncroPatch 384PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV7.1/KCNE (KVLQT/minK) current traces in response to a voltage step protocol and the corresponing current-voltage relationship plot. Using the perforated patch methodology (Escin) in combination with multi-hole chips (4 holes per well), stably transfected cells were measured on the SyncroPatch 384PE. The IC50 value of Chromanol 293B was determined as 3.82 µM. The success rate of valuable data for the analysis was 100%. 

KV4.3/KChIP2 - Dose-response curve of Flecanaide

icon sp96   170922 KV4.3 Data SyncroPatch384PESyncroPatch 384PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV4.3/KChIP2 current traces in response to a voltage step protocol and the corresponing current-voltage relationship plot. Using whole cell mode in combination with multi-hole chips (4 holes per well), stably transfected cells were measured on the SyncroPatch 384PE. The IC50 value of flecanaide was determined as 28.3 µM which is in accordance to literature. The success rate of valuable data for the analysis was 100%. 

CaV1.2 - Stable recording from frozen stock cells

icon sp96   170922 CaV1.2 Data SyncroPatch384PESyncroPatch 384PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hCaV1.2β2/α2δ1 current traces in response to a voltage step protocol and the corresponing current-voltage relationship plot. Measured on the SyncroPatch 384PE using perforated patch methodology (Escin) and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was 100 %. The cells were used from a frozen cell stock (after induction) and recorded stably for more than 20 minutes. The IC50 value of Nifedipine was determined as 21 nM.

アプリケーションノート

Cardiac Ion Channels - "High Throughput Screening of Cardiac Ion Channels"

icon sp96   SyncroPatch 384PE   icon pl   Patchliner   Icon CE   CardioExcyte 96 application note   logo pdf   (2.3 MB)

Cardiac Ion Channels - "Simultaneous Assessment of CiPA Stipulated Ion Channels on the SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (1.3 MB)
Cells were kindly provided by Charles River.

Cardiomyocytes - "Combining automated patch clamp, impedance and EFP of hiPSC-CMs"

Icon CE   CardioExcyte 96   icon sp96   SyncroPatch 3984PE   icon pl   Patchliner Application Note 
Cells kindly provided by Takara-Clonetech.

Cardiomyocytes - "Impedance and EFP recordings of Cor.4U cells using Nanion’s CardioExcyte 96"

Icon CE   CardioExcyte 96 Application Note   logo pdf   (1.3 MB)
Cells were kindly provided by Ncardia.  

Cardiomyocytes - "Impedance and EFP recordings of iCell Cardiomyocytes² on the CardioExcyte 96"

Icon CE   CardioExcyte 96 Application Note   logo pdf   (2.8 MB)
Cells were kindly provided by Cellular Dynamics.

Cardiomyocytes - "Impedance and EFP recordings of Pluricyte Cardiomyocytes on the CardioExcyte 96"

Icon CE   CardioExcyte 96 Application Note   logo pdf   (1.3 MB)
Cells were kindly provided by Ncardia.

CaV1.2 - "High Throughput Pharmacology of CaV1.2 Channels on Nanion’s SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note:   logo pdf   (2.7 MB)
Cells were kindly provided by SB Drug Discovery.  

CaV1.2 - "Stability and Pharmacology of CaV1.2 Channels on Nanion’s SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (5.3 MB)
Cells were kidly provided by Charles River.

hERG - "Effect of temperature on erythromycin action on hERG currents recorded on Nanion's Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.9 MB)
Cells were kindly provided by Millipore.

hERG - "High Throughput Pharmacology of hERG Channels on Nanion’s SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (0.6 MB)

NaV1.5 - "Characterization of CreaCell's hNaV1.5 (A-0822) on Nanion's Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.9 MB)
Cells were kindly provided by CreaCell.

NaV1.5 - "High Throughput Pharmacology of NaV1.5 Channels on Nanion's SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (1.9 MB)
Cells were kindly provided by Millipore.

NaV1.5 - "Pharmacology of hNaV1.5 recorded on Nanion's Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.3 MB)
Cells were kindly provided by Millipore.

論文

2018 - Safety Pharmacology Methods and Models in an Evolving Regulatory Environment

Icon CE   CardioExcyte 96 & CiPA Editorial in Journal of Pharmacological and Toxicological Methods (2018)

Authors:
Pugsley M.K., Harter M.L., de Korte T., Connaughton C., Authier S., Curtis M.J.

2018 - Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D)

icon sp96   SyncroPatch 384PE-related publication in International Journal of Cardiology (2018)

Authors:
Calloe K., Broendberg A.K., Christensen A.H., Pedersen L.N., Olesen M.S., de los Angeles Tejada M., Friis S., Thomsen M.B., Bundgaard H., Jensen H.K.

2018 - Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes

Icon CE   CardioExcyte 96 publication in Journal of Molecular and Cellular Cardiology

Authors: 
Wang L., Kim K., Parikh S., Cadar A.G., Bersell K.R., He H., Pinto J.R., Kryshtal D.O., Knollmann B.C.

2018 - Dehydroevodiamine and hortiamine, alkaloids from the traditional Chinese herbal drug Evodia rutaecarpa, are IKr blockers with proarrhythmic effects in vitro and in vivo

icon pl   Patchliner publication in Pharmacological Research (2018)

Authors:
Baburin I., Varkevisser R., Schramm A., Saxena P., Beyl S., Szkokan P., Linder T., Stary-Weinzinger A., van der Heyden M.A.G., Houtman M., Takanari H., Jonsson M., Beekman J.H.D., Hamburger M., Vos M.A., Hering S.

2018 - Cross-site comparison of excitation-contraction coupling using impedance and field potential recordings in hiPSC cardiomyocytes

Icon CE   CardioExcyte 96 publication in Journal of Pharmacological and Toxicological Methods (2018)

Authors:
Bot C.T., Juhasz K., Haeusermann F., Polonchuk L., Traebert M., Stölzle-Feix S.

2018 - A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of IK1 Ion Channels in Real-Time

icon pl  Patchliner publication in Frontiers in Physiology

Authors: 
Goversen B., Becker., N., Stölzle-Feix S., Obergrussberger A., Vos M.A., van Veen T.A.B., Fertig N., de Boer T.P.

2017 - L-Type Calcium Channel Inhibition Contributes to the Proarrhythmic Effects of Aconitine in Human Cardiomyocytes

icon pl  Patchliner publication in PLoS ONE (2017)

Authors: 
Wu J., Wang X., Chung Y.Y. Koh C.H. Liu Z., Guo H., Yuan Q., Wang C., Su S., Wei H.

2017 - Frequency-Dependent Multi-Well Cardiotoxicity Screening Enabled by Optogenetic Stimulation

Icon CE  CardioExcyte 96 publication in International Journal of Molecular Sciences

Authors:
Rehnelt S., Malan D., Juhasz K., Wolters B., Doerr L., Beckler M., Kettenhofen R., Bohlen H., Bruegmann T., Sasse P.

2017 - Correlation between human ether-a-go-go related gene channel inhibition and action potential prolongation

icon pl   Patchliner publication in British Journal of Pharmacology (2017)

Authors:
Saxena P., Hortigon‐Vinagre M.P., Beyl S.,Baburin I., Andranovits S., Iqbal S.M., Costa A., IJzerman A.P., Kügler P., Timin E., Smith G.L., Hering S.

2017 - Combined Impedance and Extracellular Field Potential Recordings from Human Stem Cell-Derived Cardiomyocytes 

Icon CE  CardioExcyte 96 book chapter in Stem Cell-Derived Models in Toxicology (2017)

Authors: 
Obergrussberger A., Thomas U., Stölzle-Feix S., Becker N., Juhasz K, Doerr L., Beckler M., George M., Fertig N.

2017 - Automated Patch Clamp Recordings of Human Stem Cell- Derived Cardiomyocytes.

icon pl  Patchliner and   icon sp96   SyncroPatch 384PE book chapter in Stem Cell-Derived Models in Toxicology (2017)

Authors: 
Obergrussberger A., Haarmann C., Stölzle-Feix S., Becker N., OhtsukiA., Brüggemann A., George M., Fertig N.

2017 - An impedance-based approach using human iPSC-derived cardiomyocytes significantly improves in vitro prediction of in vivo cardiotox liabilities

Icon CE  CardioExcyte 96 publication in Toxicology and Applied Pharmacology (2017)

Authors: 
Koci B., Luerman G., Duenbostell A., Kettenhofen R., Bohlen H., Coyle L., Knight B., Ku W., Volberg W., Woska Jr. J.R., Brown M.P.

2016 - Use-dependent Block of Human Cardiac Sodium Channels by GS967

icon sp96  SyncroPatch 384PE publication in Molecular Pharmacology (2016)

Authors: 
Potet F., Vanoye C.G., George Jr. A.L.

2016 - Safety pharmacology studies using EFP and impedance

Icon CE  CardioExcyte 96 publication in Journal of Pharmacological and Toxicological Methods (2016)

Authors:
Obergrussberger A., Juhasz K., Thomas U., Stölzle-Feix S., Becker N., Dörr L., Beckler M., Bot C., George M., Fertig N.

2016 - Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation

icon pl  Patchliner publication in Journal of the American College of Cardiology (2016)

Authors:
Lorberbaum T., Sampson K.J., Chang J.B., Iyer V., Woosley R.L., Kass R.S., Tatonetti N.P.

2016 - Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module

icon sp96  SyncroPatch 384PE publication in Journal of Lab Automation (2016)

Authors: 
Obergrussberger A., Brüggemann A., Goetze T.A., Rapedius M., Haarmann C., Rinke I., Becker N., Oka T., Ohtsuki A., Stengel T., Vogel M., Steindl J., Mueller M., Stiehler J., George M., Fertig N.

2016 - Automated Electrophysiological and Pharmacological Evaluation of Human Pluripotent Stem Cell-Derived Cardiomyocytes

icon pl  Patchliner publication in Stem Cells and Development (2016)

Authors: 
Rajamohan D., Kalra S., Hoang M.D., George V., Staniforth A., Russell H., Yang X., Denning C.

2015 - Novel screening techniques for ion channel targeting drugs

icon pl  Patchliner,   icon sp96   SyncroPatch 384PE and   Icon CE   CardioExcyte 96 publication in Channels (2015)

Authors: 
Obergrussberger A., Stölzle-Feix S., Becker N., Brüggemann A., Fertig N., Möller C.

2015 - New Easy-to-Use Hybrid System for Extracellular Potential and Impedance Recordings.

Icon CE  CardioExcyte 96 publication in Journal of Laboratory Automation (2015)

Authors: 
Doerr L., Thomas U., Guinot D.R., Bot C.T., Stoelzle-Feix S., Beckler M., George M., Fertig N.

2015 - Electrophysiological analysis of mammalian cells expressing hERG using automated 384-well-patch-clamp

icon sp96  SyncroPatch 384PE publication in BCM Pharmacology and Toxicology (2015) 

Authors: 
Haraguchi Y., Ohtsuki A., Oka T., Shimizu T.

2012 - Toward a new gold standard for early safety: automated temperature-controlled hERG test on the Patchliner

icon pl   Patchliner publication in Frontiers in Pharmacology (2012)

Authors: 
Polonchuk L.

2009 - High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1

icon pl  Patchliner publication in Molecular Pharmacology (2009)

Authors: 
Lewis L.M., Bhave G., Chauder B.A., Banerjee S., Lornsen K.A., Redha R., Fallen K., Lindsley C.W., Weaver C.D., Denton J.S.

ポスター

オーラルプレゼンテーション

2018 - HTS Phase I study: an update on progress of the CiPA Ion Channel Work Stream using the SyncroPatch 384PE and Patchliner

icon sp96   SyncroPatch 384PE,   icon pl   Patchliner and   Icon CE   CardioExcyte 96 Oral Presentation

Presenter: 
Tim Strassmaier, Nanion Technologies Inc. USA
Source:
Webinar: "CiPA study: Bridging ion channel and myocyte data", September 12, 2018

2018 - CiPA myocyte phase II validation study results: cross-site comparison using the CardioExcyte 96

Icon CE   CardioExcyte 96 Oral Presentation

Presenter: 
Dr. Sonja Stölzle-Feix, Nanion Technologies
Source:
Webinar: "CiPA study: Bridging ion channel and myocyte data", September 12, 2018

2017 - The CiPA initiative - Origin, Idea, Status, Issues, and Impact on Drug Development

icon pl   Patchliner Oral Presentation

Presenter: 
Dr. Herbert Himmel, Bayer Wuppertal, Germany

28.04.2015 | Webinar: Excited About Contraction – Combining Contractility and Excitability Measurements in Cardiotoxicity Screening

Icon CE   CardioExcyte 96

This Webinar covers the introduction of the CardioExcyte 96, a hybrid device for impedance- and MEA-type recordings from intact, beating networks of stem cell-derived cardiomyocytes.

12.09.2018 | Webinar: CiPA study: Bridging ion channel and myocyte data

180912 event image CiPAII Webinar

Icon CE   CardioExcyte 96,   icon pl   Patchliner and   icon sp96   SyncroPatch 384PE Webinar

Date: September 12, 4:00 PM CEST (10:00 AM EDT)

 Get up-to-date with the CiPA progress of the Myocyte and Ion Channel Work Goups:

  • CiPA myocyte phase II validation study results: cross-site comparison using the CardioExcyte 96
  • HTS Phase I study: an update on progress of the CiPA Ion Channel Work Stream using the SyncroPatch 384PE and Patchliner

製品カタログ

SyncroPatch 384/768PE - Product Sheet

icon sp96   SyncroPatch 384/768PE product sheet:   logo pdf   (0.8 MB)

Patchliner - Product Sheet

icon pl   Patchliner product sheet:    logo pdf   (2.5 MB)

CardioExcyte 96 - Product Sheet

Icon CE   CardioExcyte 96 product sheet   logo pdf   (0.7 MB)

 

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