Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Means for analyzing liquid or solid sample
Reexamination Certificate
1997-11-26
2001-05-08
Snay, Jeffrey (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Means for analyzing liquid or solid sample
C422S082060, C436S525000
Reexamination Certificate
active
06228326
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates in general to supported fluid bilayers and methods of confining them to selected areas. More specifically, the invention relates to microfabricated arrays of independently-addressable supported fluid bilayer membranes and their uses.
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BACKGROUND OF THE INVENTION
Over the last several years, a number of highthroughput screening methods have been developed to facilitate the screening of thousands, if not millions, of compounds for a desired activity or activities. Such methods are typically based on detecting the binding of a potentially effective compound to a receptor. While these binding assays are effective at constraining the universe of compounds which may have the desired activity, they are typically not well-suited for evaluating this activity with any degree of detail.
The biological activity of potentially active compounds is typically evaluated using less efficient but more informative “secondary screens” or assays which typically require a substantial input of time by a trained technician or scientist. For evaluation of candidate compounds affecting integral membrane proteins such as receptors and ion channels, the amount of time required per compound may be several hours or days if the assay includes effects on electrophysiological activity. Accordingly, there is a need for a more efficient “secondary screen” of compounds affecting the activity of such integral membrane proteins, to identify those few compounds that justify further detailed analysis.
SUMMARY OF THE INVENTION
In one aspect, the present invention includes a surface detector array device. The device includes a substrate having a surface defining a plurality of distinct bilayer-compatible surface regions separated by one or more bilayer barrier regions, a bulk aqueous phase covering the substrate surface, a lipid bilayer expanse carried on each of the bilayer-compatible surface regions, and an aqueous film interposed between each bilayer-compatible surface region and corresponding lipid bilayer expanse. In a general preferred embodiment, the bilayer-compatible surface regions and the bilayer barrier surface regions are formed of different materials.
The bilayer-compatible surface region may be formed from any of a variety of materials having such bilayer-compatible surface properties, including SiO
2
, MgF
2
, CaF
2
, and mica, as well as a polymer film, such as a polyacrylamide or dextran film. SiO
2
is a particularly effective material for the formation of a bilayer-compatible surface region.
The bilayer barrier surface region may be formed from any of a variety of materials having such bilayer barrier surface properties, including gold, positive photoresist and aluminum oxide.
In a general embodiment, the lipid bilayer expanse contains at least one lipid selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylinositol, phosphatidylglycerol, and sphingomyelin.
In one embodiment, the device contains between about 10 and about 100 distinct bilayer-compatible surface regions. In another embodiment, the device contains at least about 2500 distinct bilayer-compatible surface regions. In yet another embodiment, the device contains at least about 25,000 distinct bilayer-compatible surface regions. In still another embodiment, the device contains at least about 2.5 million distinct bilayer-compatible surface regions.
The bilayer-compatible surface regions are separated from one another, in one general embodiment, by bilayer barrier regions that are between about 1 &mgr;m and about 10 &mgr;m in width.
The lipid bilayer expanses on different bilayer-compatible surface regions may have different compositions, and may further include a selected biomolecule, wi
Boxer Steven G.
Groves Jay T.
Ulman Nick
Dehlinger Peter J.
Heinkel Gregory L.
Iota Pi Law Group
Snay Jeffrey
The Board of Trustees of the Leland Stanford Junior University
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