Membrane receptor microarrays

Membrane receptors, such as the GPCR receptors, and other 7TM membrane components, are the subject of intense cell biology and drug discovery research.  This is because 60% of all drugs work by interacting with GPCR receptors.

Membrane receptor microarrays would be the ideal tool for drug discovery, as microarrays enable entire membrane receptor families to be analyzed in a single experiment.   However because previous microarrays were unable to realistically deal with cell membrane receptors, researchers are presently forced to use expensive and slow microwell methods.  Microwell methods require large amounts of sample, and each microwell requires one or more individual operations.  As a result, at present, membrane receptor work is expensive, slow, and laborious.

Molecular Pathways has devised a novel membrane receptor microarray technology (patent 6,790,632) (text) that overcomes most of the problems associated with earlier membrane microarrays.  This new technology will enable the creation of advanced tools, such as comprehensive GPCR receptor family microarrays, that will bring new insights to many areas of modern pharmacology, biology, and medicine. 

A CIP of this patent (7,288,368)  has recently issued that extends the use of this technology into drug manufacturing process and analytical technology (PAT) applications.

Membrane-receptor microarray example:

1000 2000 nm diameter liposomes, containing fluorescent labeled membrane receptors, are bound to a transparent microarray support surface by anchor groups (not shown). The support surface is illuminated from below with fluorescent excitation light (green arrows) aimed at the correct angle to create an evanescent light wave that penetrates several hundred nanometers into the surrounding medium. The support surface also contains bound ligands (blue), which bind to the membrane receptors. In the absence of competing test ligands (left), the membrane receptors cluster close to the surface, where they receive intense evanescent excitation energy, and emit an intense fluorescent signal (red arrows). In the presence of competing test ligands (right), the membrane receptors release from the surface bound ligands, and diffuse freely over the surface of the liposome, away from the surface. The evanescent light decays rapidly with distance. These membrane receptors receive less energy, and emit a smaller signal.

The microarray is reusable, and multiple types of membrane receptors may be spotted onto different locations on a single microarray.

A speculative talk, discussing the potential use of this technology for drug discovery engines, is available here.

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