Metrion Biosciences Application notes

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Development and validation of a dual modality TREK-1 screening assay on the automated patch clamp Qube 384 platform

We report the development and optimisation of a TREK-1 functional assay using the Qube 384, an automated patch clamp platform capable of supporting high-throughput screening. The assay was optimized to identify both activators and inhibitors on the same plate, providing key mechanistic data for high value, limited supply screening libraries such as venom fractions used in this study (Targeted Venom Discovery Array, TVDA, Venomtech, UK).

CHO-K_V 1.3 and current clamp using Qube 384: another perspective of ion channel behaviour

Current clamp recordings provide more physiologically relevant measurements of ion channel activity (in comparison to voltage clamp), allowing the contribution of different ion channel sub-types to resting membrane potential to be evaluated.

Please contact us if you would like any further information regarding our suite of K_V 1.3 services or Qube screening services.

CiPA hERG Milnes kinetic assay on QPatch

To meet the FDA’s CiPA requirements for improved in silico action potential modelling and arrhythmia prediction, we have successfully created and implemented the challenging Milnes hERG cardiac safety assay

ASIC1a ligand-gated ion channel assay

Rapidly activating and desensitising ligand-gated ion channel receptors can provide a technical challenge on automated patch clamp electrophysiology platforms. This can affect their biophysics, pharmacology and assay reliability. We present data on an optimised and validated acid-activated receptor assay on the QPatch that is stable enough for drug discovery screening.

Na_V1.5(Late) cardiac safety assay on QPatch

As an alternative to standard pharmacological procedures for NaV1.5(Late) assays, we present a more reliable and accurate NaV1.5(Late) assay on QPatch that removes the requirement for activators like veratridine and ATX-II and delivers improved cardiac safety screening reliability and cost.

Na_V1.5-ΔKPQ late I_Na current properties and pharmacology on the SyncroPatch 384i

One aim of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative is to improve drug safety testing in pre-clinical development by evaluating the proarrhythmic risk of a compound. Validation studies confirm that testing the effect of compounds on an increased number of human cardiac ion channel currents including I_Na (Na_V1.5 peak and late current) as well as I_Kr (hERG) leads to improved prediction of their clinical risk.

vCor.4U™ Ventricular Enriched Cardiomyocytes: Pharmacological Characterization Utilizing Manual Patch Clamp

Introduction

Metrion Biosciences independent analysis of the spontaneous and pacing stability of vCor.4U^TM and their predictive response to selective pharmacological agents.

Abstract

Extensive cardiac ion channel profiling at Metrion using selective pharmacological tools and manual patch clamp has enabled us to define the electrophysiological characteristics of vCor.4U^TM human iPSC-derived cardiomyocytes (iPSC-CM). vCor.4U^TM elicit spontaneous action potentials (AP) and can be paced at a range of frequencies (0.2 – 1 Hz). The electrophysiological characteristics of evoked AP resemble primary human cardiomyocytes, with the cells having an
average resting membrane potential of -73 mV and action potential duration at 90 % of repolarization (APD90) of 426 ms when paced at 1 Hz.

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