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Method of determining risk of arrythmia

An arrhythmia, risk technology, used in biological testing, measurement devices, material inspection products, etc., can solve problems such as limiting the flow and duration of MEA research

Inactive Publication Date: 2013-07-24
F HOFFMANN LA ROCHE & CO AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, technical limitations limit the throughput and duration of MEA studies ((Stem Cell Research4:107-116; Stem Cell Research4:189-200)

Method used

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  • Method of determining risk of arrythmia
  • Method of determining risk of arrythmia
  • Method of determining risk of arrythmia

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Experimental program
Comparison scheme
Effect test

Embodiment

[0092] method

[0093] Chemicals

[0094] In vitro reagents were purchased from Sigma Chemical Co. (St Louis MO).

[0095] method

[0096] cell culture. Thaw hiPSC-derived cardiomyocytes (iCells) from Cellular Dynamics International (CDI) in Plating Media (CDI) and grow at 2.2–2.7 × 10 per well 6 Densities of individual cells were plated as single cells on 0.1% gelatin (Sigma)-coated 6-well tissue culture plates (Corning). At 37°C, 7% CO 2 Cells were cultured for 3-5 days, after which they were re-plated onto 96-well cardio-e-plates (ACEA / Roche Applied Sciences) or microelectrode arrays (MEA, Multichannel Systems). After plating, the medium was changed every two days using Maintenance Media (CDI) (prewarmed to 37°C to minimize temperature shock to the cells).

[0097] overview

[0098] The new RTCA cardio system allows monitoring of cellular experiments over longer time frames and measures the contraction (beating) of cells in parallel. At each measurement time point...

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Abstract

The present invention relates to a method of determining the risk of drug induced arrhythmia using stem cell derived cardiomyocytes in a high-throughput impedance or multi-electrode array assay.

Description

[0001] The present invention relates to methods for determining drug-induced arrhythmia risk using stem cell-derived cardiomyocytes using high-throughput impedance or multielectrode array assays. Background of the invention [0002] Drug-induced torsades de pointes (TdP), a life-threatening polymorphic ventricular tachyarrhythmia, has led to the withdrawal or withdrawal of many medications. Severe limitations ((Journal of Pharmacological and Toxicological Methods52:46-59, 2005). The usual cause of TdP is the repression of the inward rectifying potassium channel, hERG (the human or go-go related gene encoded by KCNH2), results in a prolonged QT interval. Currently, the standard approach is to screen drug candidates for hERG inhibition using non-cardiomyocyte cell lines that overexpress hERG. However, hERG screening is suboptimal because not all compounds that inhibit hERG channels Both cause QT prolongation or induce TdP (Cardiovascular Research 58:32-45, 2003).In addition, arr...

Claims

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Application Information

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IPC IPC(8): G01N33/68
CPCG01N33/6887G01N2800/326C12N5/06G01N27/00G01N27/128G01N33/5061
Inventor R·阿布拉姆斯J·巴比亚兹E·乔郭亮K·L·科拉雅
Owner F HOFFMANN LA ROCHE & CO AG
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