• 参与CiPA的设备

    Patchliner和SyncroPatch 384PE (CiPA离子通道工作组); CardioExcyte 96 (CiPA心肌细胞工作组)

  • CiPA hERG Protocol

    在Patchliner和SyncroPatch 384PE上进行hERG研究的protocol。

  • 高通量CiPA hERG 试验

    在SyncroPatch 384PE上使用CiPA hERG protocol记录到的Cisapride作用

  • 心肌细胞 & 离子通道作用

    iPSC分化的心肌细胞的心律失常场电位 (CardioExcyte 96) 与hERG电流抑制(SyncroPatch 384PE)

  • GΩ级封接的高通量膜片钳

    高通量记录CiPA相关的心肌离子通道

  • GΩ级封接的高通量膜片钳

    在生理温度下高通量记录心肌离子通道

  • CardioExcyte 96筛选工具

    心脏安全筛选的工具CardioExcyte 96与配套的移液器

CiPA - 综合体外致心律失常试验

综合体外致心律失常试验(The Comprehensive In Vitro Proarrhythmia Assay, CiPA)旨在代替 ICH S7B安全药理准则与临床TQT研究规定的临床前hERG电流试验。 该范式旨在提供一种致心律失常的替代指标,随着越来越多转化相关的致心律失常风险评估 (Sager et al., 2014)。CiPA打算通过对与尖端扭转型室速 (TdP) 与 QT间期延长关联的致心律失常的电生理机制的理解,来实现评价候选药物的致心律失常风险评估。


CiPA工作流程

CiPA Work Groups

综合体外致心律失常试验(The Comprehensive In Vitro Proarrhythmia Assay, CiPA)开始于2013年,领导小组成员来自美国FDA, HESI, CSRC, SPS, Japan NIHS, PMDA, EMA和Health Canada。 A number of participating organizations, amongst them Nanion Technologies, build the backbone of the initiative. CiPA工作流程包括:In Silico, Myocyte, Ion ChannelClinical Translation 工作组。

Nanion是离子通道高通量组的委员会成员,同时也参与了心肌细胞工作组。Nanion在心脏离子通道的全自动膜片钳筛选方面进行了多年的研究并具有经验。我们也有非标记记录干细胞来源的心肌细胞 (iPSC-CMs)收缩与场电位的设备。我们的设备在全球主流的药企与 CRO公司被广泛用于安全筛选,我们也很乐意协助您开始您的CiPA试验。


第一阶段研究结果

CiPA Table Phase I small离子通道工作组在2017年完成了第一阶段的研究,Nanion技术的德国总部、美国与日本的分公司使用Patchliner与SyncroPatch 384PE参与了该研究。

左图展示了12种化合物对hERG的阻断效应。该结果与手动膜片钳得出的数据 (Crumb et al., 2016)高度一致。


CiPA工作流程中的Nanion设备


icon sp96   SyncroPatch 384/768PE -高通量全自动膜片钳

Nanion CiPA IconSyncroPatch 384PE (可升级至768PE) 是一款最高可同时记录384 (or 768)个细胞的高通量膜片钳系统。SyncroPatch 384/768PE是目前全球最高通量的实现GΩ封接数据质量的膜片钳产品。SyncroPatch 384PE参与了CiPA离子通道工作组的研究。
点击获取SyncroPatch 384PE的CiPA试验方法

icon pl   Patchliner - 兼顾科研与药筛的膜片钳系统

Nanion CiPA Icon Patchliner 是一款全自动平板膜片钳设备,可以支持最多同时记录8个细胞。Patchliner有着极高的实验灵活度和GΩ级封接的数据质量,是市场上最全能的膜片钳设备。 
Patchliner参与了CiPA离子通道工作组的研究。
点击获取Patchliner的 CiPA试验方法。 

Icon CE   CardioExcyte 96 - 结合细胞收缩、电生理记录与细胞活力测量

Nanion CiPA Icon CardioExcyte 96  是一款结合心肌细胞网络收缩与电生理记录的设备,同时该设备可以持续自动记录细胞的基础阻抗,该参数可用于测量短期与长期的细胞活性。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. 
CardioExcyte 96 参与了 CiPA心肌细胞工作组 的研究。
点击获取CardioExcyte 96 CiPA试验方法

离子通道工作组(Ion Channel Work Group,ICWG)

ICWG: 介绍与历史

"The Ion Channel Working Group (ICWG), sponsored by the Safety Pharmacology Society (SPS), was established in December 2013. Its primary role is to work in close collaboration with the In Silico Working Group (ISWG) in providing ion channel support for the development of a computer model of the adult human ventricular myocyte, to be used as part of the CiPA initiative in predicting the clinical risk of drug-induced TdP."

"The original remit of the ICWG was: 1) to select key cardiac ion channels to include in the CiPA evaluation; 2) to develop robust, reliable and reproducible voltage clamp protocols required to generate data allowing the training and validation of the in silico model; 3) to define which biophysical and/or pharmacological properties of the channels to study for drug effects in order to optimize the predictivity of the model (e.g., potency (IC50), kinetic of block, rate/use/voltage dependence) and; 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) ")


离子通道工作组进展

"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")


CiPA离子通道工作组研究的6个离子通道的数据、应用和文献

肌细胞工作组(Myocyte Work Group,MWG)

MWG: 介绍与历史

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) ")


肌细胞工作组进展

"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公司参与CiPA的内容:

数据与应用

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.

应用文献

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.

发表文献

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.

海报

公开演讲

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 | 在线研讨会: 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

日期: 9月12日, 4:00 PM CEST (北京时间10:00 PM)

 获取CiPA肌细胞与离子通道工作组的最新进展:

  • CiPA 肌细胞第二阶段验证研究结果:: cross-site comparison using the CardioExcyte 96
  • 高通量第一阶段研究: an update on progress of the CiPA Ion Channel Work Stream using the SyncroPatch 384PE and Patchliner

设备产品单页

SyncroPatch 384/768PE - 产品单页

icon sp96   SyncroPatch 384/768PE 产品单页:   logo pdf   (7.6 MB)

Patchliner - 产品单页

icon pl   Patchliner 产品单页:    logo pdf   (0.8 MB)

CardioExcyte 96 - 产品单页

Icon CE   CardioExcyte 96 产品单页   logo pdf   (2.6 MB)

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