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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

icon sp96   SyncroPatch 384PE and   icon pl   Patchliner poster, FENS Meeting 2018  logo pdf   (2.5 MB)

2017 - Activation of CFTR channels in absence of internal fluoride using a highly parallel automated patch clamp system

icon sp96   SyncroPatch 384PE poster, BPS Meeting 2017  logo pdf   (1.5 MB)

2017 - Pharmacological Characterization of the NMDA A-B-C by Automated Patch Clamp

icon sp96   SyncroPatch 384PE poster, BPS Meeting 2017  logo pdf   (4.9 MB)

2017 - lnvestigation of the Ion Channels hTMEM16A/Ano1 and TRPC5 and their Modulation by Intracellular Calcium

icon sp96   SyncroPatch 384PE poster, BPS Meeting 2017  logo pdf   (1.3 MB)

NaV1.8 - State Dependent Inhibition

icon sp96   PE NaV1.8 State dep InhibitionSyncroPatch 384PE 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

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 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.

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.

2018 - High throughput automatic patch clamp: Applications for Safety Pharmacology

icon sp96   SyncroPatch 384PE poster, JSPS Meeting 2018  logo pdf   (2.3 MB)

2018 - Biophysical and Pharmacological Characterization of Voltage-Gated Sodium Channels Involved in Pain Pathways

icon sp96   SyncroPatch 384PE Oral Presentation Video

Presenter: 
Dr. Markus Rapedius, Senior Scientist, Nanion Technologies

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).

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).

2017 - HTS in Cardiac Safety

Icon CE   CardioExcyte 96 presentation (slide deck)   logo pdf   (4.0 MB)

27.06.2017 | Webinar: New Dynamics in Automated Patch Clamp

icon pl   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

Icon Orbit Mini   Orbit mini,   Icon CE   CardioExcyte 96 and   icon sp96   SyncroPatch 384PE poster, Meeting of the French Society of Toxinology (SFET) 2015  logo pdf   (0.9 MB)

TRPC5 - "Internal perfusion of Ca2+ to activate hTRPC5 on Nanion's SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (1.7 MB)
Cells were kindly provided by Charles River.

CFTR - "Different modes of activation of CFTR recorded on Nanion’s SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (5.7 MB)

NaV1.8 - "Stability and reproducibility of hNaV1.8 recordings on Nanion's SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (1.4 MB)
Cells were kindly provided by Charles River.

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.

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. 

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.

KCa3.1 - "Modulation of hKCa3.1 by internal Ca2+ performed on Nanion’s Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.6 MB)
Cells were kindly provided by Charles River.

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.

NMDA Receptors (NR1/NR2A & NR1/NR2B) - "Activation and Inhibition of human NMDA Channels on Nanion`s SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (3.0 MB)
Cells were kindly provided by Charles River.

TRPM8 - "TRPM8 activation by menthol and Eucalyptol performed on Nanion’s Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.4 MB)
Cells were kindly provided by Charles River.

KV1.5 - Dose response curve of 4-AP

icon sp96   KV1.5 Data 3845PESyncroPatch 384PE 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

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.

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%. 

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%. 

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.

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 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.

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