Metrion Biosciences Cardiac Safety Screening Services
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Cardiac Translational Manual Patch Assays

Metrion offers a set of reliable and reproducible translational human cardiovascular assays to demonstrate the cardiac safety of your therapeutic compounds in line with current and future CiPA and FDA guidelines.

Our approach

High quality cardiac toxicity data generation and interpretation is vital to the efficient progression of a drug discovery campaign. Metrion offers a range of translational, phenotypic cardiac assays and platforms that have been validated using a number of commercially available human iPSC-derived cardiomyocyte cell lines.  Using technologies such as manual patch clamp electrophysiology, multi-electrode array (MEA; Maestro platform) or dual MEA/impedance readouts (CardioExcyte96), Metrion can offer a direct readout of physiological function and cardiac risk in the iPSC-derived cardiomyocyte cell line- of your choosing.

Manual Patch Assays

Metrion has considerable expertise working with human iPSC-derived cardiomyocytes on the manual patch clamp platform. The company has access to, and has characterised, a wide range of commercially available cell lines from a number of vendors. Metrion offers services to screen compounds against action potentials and membrane currents recorded from iPSC-derived cardiomyocytes. Furthermore, we provide a cell line characterisation service for companies and vendors looking to commercialise their cell lines.

Stimulated Action Potentials

Stable action potential recordings can be taken for up to one hour using stimulation via a bath field electrode or current injection through the recording pipette. These long-term recordings enable application of multiple concentrations of a compound during a single experiment (see panel below). Frequency-dependent effects on action potential parameters can also be investigated in this assay format.

Figure 1a stimulated AP DMSO control
Figure 1a. Stimulated AP (DMSO control)
Figure 1b stimulated AP DMSO control
Figure 1b. Stable AP parameters in DMSO
Figure 1c stimulated AP DMSO control
Figure 1c. Measured AP parameters

CiPA Toolbox Compounds

Our testing of CiPA toolbox compounds can help identify and quantify the roles of key cardiac ion channels underlying the action potential in human cardiomyocytes, and thus to benchmark the effects and cardiac risk profile of new test compounds. For example, exposure to the hERG inhibitor dofetilide results in action potential prolongation, arrhythmogenesis and early after depolarisations (EADs), validating the proarrhythmic effect of a Torsadogenic compound in our in vitro assays. 

Figure 2a Stimulated example figures
Figure 2a. Effect of Lidocaine on AP
Figure 2b Stimulated example figures
Figure 2b. Effect of Nifedipine on AP
Figure 2c Stimulated example figures
Figure 2c. Effect of Dofetilide on AP

Spontaneous Action Potential Recordings

iPSC-derived cardiomyocytes possess intrinsic pacemaker activity, resulting in spontaneous action potential firing. This allows us to determine the effect of a test compound on action potential firing frequency and to identify compounds with the potential to slow (bradycardia) or increase (tachycardia) heart rate in vivo. Metrion has tested a toolbox of compounds with cardiac activity and confirmed their anticipated effect on spontaneous action potential parameters, which were consistent with those determined from stimulated cells. For example, the hERG blocker dofetilide significantly prolonged the action potential duration of iPSC-derived cardiomyocytes and induced EADs (see Figures below).

Figure 5a Landscape EAD
Figure 3a. Spontaneous iPSC cardiac APs
Figure 5b Landscape EAD
Figure 3b. Dofetilide induces EAD arrythmia

Voltage Clamp Assays

Metrion has validated voltage clamp assays to quantify activity of a range of ion channels expressed in iPSC-derived ventricular and atrial cardiomyocytes. Metrion can determine the expression density of such currents as part of an in-depth service to characterise new cell lines. Voltage clamp studies using either iPSC-derived cardiomyocytes or cell lines expressing recombinant ion channels can also be used to support phenotypic and modelling predications as part of an integrated CiPA approach.

Figure 6. INav
Figure 4a. Voltage-activated Nav currents
Figure 7 Voltage clamp INav IV
Figure 4b. INav IV curve
Figure 8 Manual Patch currents
Figure 4c. Ventricular and atrial currents

Translational Cardiac Assays Resource Library

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Let’s work together

What are your specific ion channel screening requirements?

If you have any questions, or would like to discuss your project, we will put you directly in touch with a member of our scientific team. Contact us today to discover more.