Method for Drug Screening and Characterization by Calcium Flux Analysis

Tech ID: ben000015

Introduction

Ion channels participate in, and regulate, cellular processes as diverse as the generation and timing of action potentials, energy production, synaptic transmission, and secretion of hormones and the contraction of muscles. In fact, many drugs exert their specific effects via modulation of ion channels. One example of ion oscillation occurs in calcium (Ca2+) channels, which are generally found in many cells where, among other functions, they play important roles in signal transduction. In excitable cells, intracellular calcium supplies a maintained inward current for long depolarizing responses and serves as the link between depolarization and other intracellular signal transduction mechanisms.

This method allows for measuring of calcium flux on images and plotting it for each dose of the agent being tested and at the single cell level. It then allows for transformation of these plots into dose response curves for individual cells and allows for aggregated data analysis. This provides a means of measuring statistical variability of cell populations for improved screening and development methods of drugs.

Technology Description

The method is based on imaging and measuring single cell dose response via fluorescent ion dyes. It records individual cell responses to drug doses. Dose response curves and other pharmacological parameters are computed by measuring changes in oscillation for each drug dose and each individual cell.

Variance in pharmacological response in cell populations under the same experimental conditions is normal among cells and therefore a statistically meaningful measurement of cellular responses and statistically significant variability of response in cell populations is considered more meaningful and impart high confidence in results when screening for drugs or testing other agents

Advantages/Novelty

• The conventional measurement in early drug discovery assays was radioactivity. However, the need for more information, higher throughput and miniaturization has caused a shift towards using fluorescence detection.

• Fluorescence-based reagents can yield more powerful, multiple parameter assays that are higher in throughput and information content and require lower volumes of reagents and test compounds.

• Fluorescence is also safer and less expensive than radioactivity-based methods.

Applications

• The software can be further developed to accompany any existing drug screening system measuring fluorescence.

• The technology can be incorporated into current drug screening systems to fit the constantly increasing need of compound screening in drug development.

Intellectual Property

US patent US 8,709,804  granted.  

Patent Information:
Category(s):
Tool
For Information, Contact:
Wenyue Du
Senior Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
Anat BeN-Shlomo
Shlomo Melmed
Kolja Wawrowsky
Keywords:
Drug Discovery/Screening
Research