Data analysis of cells undergoing excitation contraction coupling as detected on real-time cell analysis (RTCA) instruments

Abstract

A method of determining a beating parameter of cells that undergo excitation contraction coupling, the method including providing a cell analysis device having a substrate and a sensor that measures cell adhesion or attachment to the substrate in millisecond time resolution; adding excitable cells capable of undergoing excitation contraction coupling to the substrate; monitoring cell adhesion or attachment of the excitable cells to the substrate in millisecond time resolution; and calculating one or more beating parameters from the monitored adhesion.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This is a continuation of U.S. Ser. No. 13 / 109,809, filed May 17, 2011, which is a continuation in part of U.S. patent application Ser. No. 12 / 435,569, filed on May 5, 2009, which claims benefit of priority to U.S. provisional patent application Ser. No. 61 / 191,684, filed on Sep. 11, 2008 and U.S. provisional patent application Ser. No. 61 / 126,533, filed on May 5, 2008, the contents of each are herein incorporated by reference in their entirety.[0002]U.S. Ser. No. 13 / 109,809 also claims benefit of priority to U.S. provisional patent application Ser. No. 61 / 345,867 filed on May 18, 2010; the contents of which are herein incorporated by reference in their entirety.TECHNICAL FIELD[0003]The invention relates to cell based assays that monitor excitation contraction coupling of cells and more specifically to methods for determining cell beating parameters by monitoring cell adhesion or attachment of cells that undergo excitation contraction cou...

AI Technical Summary

Benefits of technology

The invention is a method for studying cardiomyocytes and their response to therapeutic agents by measuring their beating parameters. The method involves adding cardiomyocytes to a device that can measure their beating in millisecond time resolution, such as an impedance monitoring device or an optical sensor, and collecting data on their beating for analysis. The beating parameters of interest include beating rate, beating amplitude, rising time, falling time, beating period, and others. The method can be used to identify changes in beating parameters caused by test compounds and to assess their potential cardiotoxicity. The technical effect of the invention is to provide a reliable and efficient tool for studying cardiomyocytes and their response to drugs or chemical compounds.

Problems solved by technology

Since 1981, at least 10 blockbuster drugs have been withdrawn from the market due to cardiac liability, defined as potentially undesirable effects on heart function.

These drugs are thought to disrupt iron metabolism, generating harmful oxygen radical species which ultimately cause mitochondrial damage and apoptosis.

Disturbances in the ionic movement of interference with ion channel activities may lead to arrhythmia.

ERG channel blockage may lead to QT elongation and this may cause a fatal form of ventricular arrhythmia called Torsades de Pointes (TdP).

However, this approach suffers from being extremely labor-intensive, time consuming and costly and at the same time not very amenable to the high throughput demands of pharmaceutical industry.

However, use of this method in high throughput requires automation of patch clamping in an array format with reliable giga seal, which even though is becoming increasing available, is not yet widespread.

In addition, cardiac toxicity may occur by other mechanisms that could be possibly missed by this type of targeted approach.

Even though high throughput to medium throughput systems have been developed for functional characterization of cell lines heterologously expressing the gene for specific ion channels, high throughput techniques for functional characterization of more complex systems such as cardiomyocytes have been limited.

High throughput techniques for short term functional characterization of ion channels and other targets in cardiomyocytes has been rather challenging and limited.

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