Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Polymers from only ethylenic monomers or processes of...
Reexamination Certificate
2001-05-16
2004-04-20
Seidleck, James J. (Department: 1711)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Polymers from only ethylenic monomers or processes of...
C526S303100, C526S297000, C526S291000, C526S317100, C526S310000, C526S308000, C526S307400, C526S318000, C526S318250, C526S318410, C526S332000, C526S335000, C526S346000, C526S348000, C522S060000, C522S031000, C522S084000, C522S086000, C522S087000, C522S091000, C522S096000, C522S148000, C522S172000, C522S150000, C522S151000, C522S152000, C522S153000, C522S154000, C522S157000, C522S173000, C522S178000, C522S181000, C522S182000
Reexamination Certificate
active
06723814
ABSTRACT:
FIELD OF THE INVENTION
The present invention is generally in the field of planar membranes. More specifically, the invention is in the field of planar membranes made with self-assembling amphiphilic segmented copolymers.
BACKGROUND OF THE INVENTION
Self-organizing, or self-assembling, structures are known. A common example is liposomes. Liposomes are made by emulsifying amphiphilic (and optionally hydrophobic or lipophilic) molecules in water, preferably in the presence of surfactant. Liposomes are either unilamellar or multilamellar spheres that are manufactured from a variety of lipids. Drugs, for example, can be encapsulated within liposomes or captured within the liposome membrane. Other types of self-assembling structures include planar lipid membranes, which are termed Black Lipid Membranes in the art. Membranes are preferred over liposomes for applications where a flat surface is desired such as, for example, matrices for biological sensors.
Self-assembled structures known in the prior art have often exhibited limited stability. Cross-linked liposomes have been prepared which are more resistant to degradation. Liposomes having “pegylated” surfaces, i.e., surfaces having coated thereon or bonded thereto polyethylene glycol, have longer circulating times following administration to a patient. Other methods to prepare liposomes with enhanced stability include preparation techniques such as emulsion polymerization and interfacial polymerization. However, these techniques require rather aggressive reaction conditions, so sensitive substances cannot be used during these procedures. The stability of liposomes can be enhanced by surface grafting of hydrophilic polymers or by polymerization of reactive lipid molecules in the vesicular aggregates. Recently, a similar mechanical stabilization of vesicles was obtained by swelling the lipid bilayer of vesicles with hydrophobic monomers, which were subsequently polymerized.
Lipid bilayers are the basic constituent of biological membranes. The lipids serve as a fluid matrix for many membrane associated proteins responsible for various key functions such as signaling or transport. Many of these membrane proteins are pharmacologically important or have biotechnological potential. It would be advantageous to have an artificial membrane system in which they and other biological molecules can be immobilized. Such a system would provide a number of benefits, including the ability to use the immobilized protein in biosensors.
SUMMARY OF THE INVENTION
Membranes are made from segmented amphiphilic A+B copolymers, where A is hydrophilic and B is hydrophobic, which self-assemble when dispersed in water. In one embodiment, the membranes are freestanding, where the term “freestanding” refers to a membrane that is not supported on a substrate. In another embodiment, the membranes are supported on a substrate. In a preferred embodiment, the copolymer is a segmented copolymer, such as a triblock ABA copolymer. The segmented copolymer forms a membrane where the middle layer is hydrophobic, and the outer layers are hydrophilic. In another embodiment, the copolymer is a BAB copolymer. The membranes may be stabilized by end-group polymerization and/or by crosslinking of internal groups. The polymerization and crosslinking can be achieved via ionic bonds, covalent bonds, and/or through other types of bonds. In one embodiment, end groups of the copolymers are polymerized. Polymerization can achieved by any of a number of means, including photopolymerization, typically in the presence of a photoinitiator. Other types of polymerization are also possible, such as redox polymerization. In one embodiment, the membranes include proteins, such as membrane proteins, that allow the transport there through of selected components.
In general, planar membranes with a thickness ranging from about 1 to 100 nm, in one embodiment on the order of about 10 nm, can be prepared from a triblock amphiphilic copolymer. Stable films with areas from about 10 nm
2
to 10 cm
2
, generally up to about 1 mm
2
can be made. The triblock copolymer can have polymerizable groups at both chain ends and/or at internal sites. These groups can be polymerized, by UV light, for example, after the formation of the self-assembled membrane. The mechanical properties of the membranes, as characterized by short electric fields, are significantly more cohesive than lipid bilayers, as seen by the higher critical voltages required for rupture. Polymerization further increases the stability of the membranes.
Molecules can be reconstituted in the block copolymer membranes. In one embodiment the molecule is a lipid membrane protein. The protein remains functional in the completely artificial surrounding even after polymerization of the membrane.
The materials disclosed herein could be used for a number of purposes, such as biosensors, non-linear optical devices, coatings, in diagnostics, for drug delivery, and for other applications.
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Meier Wolfgang
Nardin Corinne
Winterhalter Mathias
Beard Collen A.
BioCure, Inc.
McClendon Sanza L
Seidleck James J.
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