Collaborative Activities and projects with Charles River
NaV1.5-Late - "INa-Late recorded from CHO cells and hiPSC-CMs on Nanion´s Patchliner"
Patchliner application note: 
(0.5 MB)
Cells were kindly provided by Charles River.
iCell® Cardiomyocytes2 were kindly provided by Fujifilm Cellular Dynamics International.
NaV1.5 - Raw current traces and Current-Voltage Relationship
Port-a-Patch mini data and applications:
Cells were kindly provided by Charles River.
The image shows currents from an example cell and the corresponding current-voltage plot for NaV1.5 expressed in stably-transfected CHO-K1 cells.
NaV1.5 - Tetracaine concentration response curve
Port-a-Patch mini data and applications:
Cells were kindly provided by Charles River.
The image shows the timecourse of the experiment (top) where peak amplitude is plotted against time and example traces in control conditions and different concentrations of tetracaine are also shown in the insert. The concentration reponse curve for tetracaine is shown on the bottom for an average of 6 cells. The curve is fit with a Hill equation revealing an IC50 = 25.5 ± 5.7 µM (n = 6).
NaV-Late - Recorded from Cardiosight-S hiPSC-CMs
Port-a-Patch mini data and applications:
Cells were kindly provided by Nexel.
NaV-Late was induced by application of ATX II in Cardiosight-S® cells on the Port-a-Patch mini. Example traces are shown on the top with the response to the voltage ramp (CiPA protocol) shown in the inset. The timecourse of the experiment is shown on the bottom, with block by ranolazine.
26.09.2018 | Nanion Technologies places two SyncroPatch 384PE Instruments for Ion Channel Screening at Charles River Laboratories
LIVINGSTON, N.J., MUNICH, Germany, September 26, 2018: Nanion announced today that Charles River Laboratories has purchased two SyncroPatch 384PE high-throughput patch clamp instruments. This purchase reflects an investment in screening technologies and assay development, while accommodating the rising demand in contract service for globally shared clients. The instruments will be delivered to Charles River (Cleveland site; former ChanTest) in November of this year and will be used for various ion channel screening & profiling services, including cardiac safety screening, efficacy, and SAR studies.
2018 - Investigating pain pathways by inhibition of voltage-gated sodium channels
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) and Patchliner poster, FENS Meeting 2018 (2.5 MB)
2017 - Activation of CFTR channels in absence of internal fluoride using a highly parallel automated patch clamp system
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) poster, BPS Meeting 2017 (1.5 MB)
2017 - Pharmacological Characterization of the NMDA A-B-C by Automated Patch Clamp
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) poster, BPS Meeting 2017 (4.9 MB)
2017 - lnvestigation of the Ion Channels hTMEM16A/Ano1 and TRPC5 and their Modulation by Intracellular Calcium
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) poster, BPS Meeting 2017 (1.3 MB)
NaV1.8 - State Dependent Inhibition
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.
The state dependent inhibition of Tetracaine on NaV1.8 currents were investigated. Measured on the SyncroPatch 384PE the perforated cell patch methodology (Escin) and multi-hole chips were used and compared to single-whole chips. Using a state dependant pulse protocol, the IC50 value determined from the first pulse (C1) was calculated as 54.3 µM (Hill coefficient = 1.50), and from the second pulse (C2) as 1.27 µM (Hill coefficient = 0.62).
NaV1.5 - Late Current Analysis using the CiPA Protocol
SyncroPatch 384/768 PE (a predecessor model of the SyncroPatch 384/768i) 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
SyncroPatch 384/768 PE (a predecessor model of the SyncroPatch 384/768i) 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
SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) 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
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) 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
Patchliner 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
SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) 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
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) 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 Vandetanib
CardioExcyte 96 and 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.
Cardiac Ion Channels - Pharmacology of Sotalol
CardioExcyte 96 and SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) 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.
2018 - High throughput automatic patch clamp: Applications for Safety Pharmacology
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) poster, JSPS Meeting 2018 (2.3 MB)
2018 - Biophysical and Pharmacological Characterization of Voltage-Gated Sodium Channels Involved in Pain Pathways
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Oral Presentation Video
Presenter:
Dr. Markus Rapedius, Senior Scientist, Nanion Technologies
Kir2.1 - Pharmacology of Barium
SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) 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).
KV4.3 - Pharmacology of Quinidine
SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) 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).
2017 - HTS in Cardiac Safety
CardioExcyte 96 presentation (slide deck) (4.0 MB)
27.06.2017 | Webinar: New Dynamics in Automated Patch Clamp
Patchliner
This webinar shows new applications on dynamic patch clamp of iPSC-derived cardiomyocytes and introduces an assay on KCa3.1 expressed in erythrocytes
2016 - Next level toxicity screening: From single channel to overall cell behavior
Orbit mini, CardioExcyte 96 and SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) poster, Meeting of the French Society of Toxinology (SFET) 2015 (0.9 MB)
TRPC5 - "Internal perfusion of Ca2+ to activate hTRPC5 on Nanion's SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) application note (1.7 MB)
Cells were kindly provided by Charles River.
CFTR - "Different modes of activation of CFTR recorded on Nanion’s SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note (5.7 MB)
NaV1.8 - "Stability and reproducibility of hNaV1.8 recordings on Nanion's SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note (1.4 MB)
Cells were kindly provided by Charles River.
2015 - Novel screening techniques for ion channel targeting drugs
Patchliner, SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and CardioExcyte 96 publication in Channels (2015)
Authors:
Obergrussberger A., Stölzle-Feix S., Becker N., Brüggemann A., Fertig N., Möller C.
hERG - Stable Recordings with Accurate Pharmacology
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) 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.
Cardiac Ion Channels - "Simultaneous Assessment of CiPA Stipulated Ion Channels on the SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note (1.3 MB)
Cells were kindly provided by Charles River.
KCa3.1 - "Modulation of hKCa3.1 by internal Ca2+ performed on Nanion’s Patchliner"
Patchliner application note: (0.6 MB)
Cells were kindly provided by Charles River.
CaV1.2 - "Stability and Pharmacology of CaV1.2 Channels on Nanion’s SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note (5.3 MB)
Cells were kidly provided by Charles River.
NMDA Receptors (NR1/NR2A & NR1/NR2B) - "Activation and Inhibition of human NMDA Channels on Nanion`s SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note (3.0 MB)
Cells were kindly provided by Charles River.
TRPM8 - "TRPM8 activation by menthol and Eucalyptol performed on Nanion’s Patchliner"
Patchliner application note: (0.4 MB)
Cells were kindly provided by Charles River.
KV1.5 - Dose response curve of 4-AP
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.
Screenshots of the PatchControl 384 software showing a dose-response curve of 4-AP on KV1.5 stably transfected cells. Measured on the SyncroPatch 384PE using multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was 100%. The IC50 value of 160 µM measured on the SyncroPatch 384PE corresponds well to literature (IC50 4-AP: 270 µM; Gutman et al., Pharmacological Reviews 57: 473-508, 2005).
CaV1.2 - Stable recording from frozen stock cells
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) 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.
KV4.3/KChIP2 - Dose-response curve of Flecanaide
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) 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%.
KV7.1 (KVLQT) - Dose-response curve
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) 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%.
hERG - Pharmacology of Bepridil, Dofetilide, Cisapride, Diltiazem (Results CiPA Phase I Study)
Patchliner 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.
hERG - Pharmacology of Mexiletine, Quinidine, Ondansetron, Ranolazine (Results CiPA Phase I Study)
Patchliner 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 Sotalol, Terfenadine, Verapamil (Results CiPA Phase I Study)
Patchliner 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.