US4035316A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Cell specific, variable density, polymer microspheres
Assignee: California Institute of Technology
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Filing: 1975-11-24
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Granted: 1977-07-12
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Expires: 1995-11-24
Abstract
Abstract Biocompatible polymeric microspheres having an average diameter below about 3 microns and having density at least 15% greater or lesser than organic cells and having covalent binding sites are provided in accordance with this invention. The microspheres are obtained by copolymerizing a hydroxy or amine substituted acrylic monomer such as hydroxyethylmethacrylate with a light or dense comonomer such as a fluoromonomer. A lectin or antibody is bound to the hydroxy or amine site of the bead to provide cell specificity. When added to a cell suspension the marked bead will specifically label the cell membrane by binding to specific receptor sites thereon. The labelled membrane can then be separated by density gradient centrifugation.
Inventors
- 👤 Shiao-Ping S. Yen
- 👤 Alan Rembaum
- 👤 Robert S. Molday
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:23
CPC Classifications
C; C08; C08F; C08F220/00; C08F220/02; C08F220/10; C08F220/34; C08F220/20; Y; Y10; Y10S; Y10S436/00; Y10S436/80; Y10S436/804; Y10S436/827; Y10S526/00; Y10S526/909; Y10S526/936; Y10S530/00; Y10S530/806; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
91 words
A composition consisting essentially of a suspension of polymeric beads having an average diameter below 5 microns, having a density less than 1.15 g/cc or greater than 1.30 g/cc and comprising the cross-linked product of an ethylenically unsaturated monomer mixture including at least 10% by weight first ethylenically unsaturated monomer containing at least one substituent selected from hydroxyl, carboxyl or amino, at least 25% by weight of a second ethylenically unsaturated comonomer having a density differing from the first monomer by at least 15%, and 1-20% of a polyunsaturated cross-linking agent.
Claim 2
Dependent Claim
91 words
A composition consisting essentially of a suspension of polymeric beads having an average diameter below 5 microns, having a density less than 1.15 g/cc or greater than 1.30 g/cc and comprising the cross-linked product of an ethylenically unsaturated monomer mixture including at least 10% by weight first ethylenically unsaturated monomer containing at least one substituent selected from hydroxyl, carboxyl or amino, at least 25% by weight of a second ethylenically unsaturated comonomer having a density differing from the first monomer by at least 15%, and 1-20% of a polyunsaturated cross-linking agent.
Claim 3
Dependent Claim
29 words
A composition according to claim 1 in which the first monomer is a substituted acrylic monomer present in the mixture in an amount from 20 to 60% by weight.
Claim 4
Dependent Claim
30 words
A composition according to claim 2 in which the beads are hydrophilic, swellable, porous, uniformly shaped round beads, at least 80% of which have a uniform diameter below 3 microns.
Claim 5
Dependent Claim
26 words
A composition according to claim 3 in which the first monomer is selected from acrylamide, hydroxy-lower alkyl acrylates, amino-lower alkyl acrylates, acrylic acid or methacrylic acid.
Claim 6
Dependent Claim
62 words
A composition according to claim 4 in which the first monomer is selected from compounds of the formula: ##STR2## where R 1 is hydrogen or lower alkyl of 1-8 carbon atoms, R 2 is alkylene of 1-12 carbon atoms, Z is OH or R 3 --N 1 --R 4 where R 3 or R 4 are H, lower alkyl or lower alkoxy.
Claim 7
Dependent Claim
20 words
A composition according to claim 5 in which the first monomer is selected from 2-hydroxyethyl methacrylate, 3-hydroxypropyl-methacrylate, 2-dimethylaminoethylmethacrylate and 2-aminoethylmethacrylate.
Claim 8
Dependent Claim
41 words
A composition according to claim 2 in which the cross-linking agent is a polyvinyl diene or triene capable of addition polymerization with the first monomer and comonomer and is present in the monomer mixture in an amount from 5-15% by weight.
Claim 9
Dependent Claim
24 words
A composition according to claim 7 in which the cross-linking agent is selected from ethylene glycol dimethacrylate, divinyl benzene, trimethylol propane trimethacrylate, and N,N'-methylene-bis-acrylamide.
Claim 10
Dependent Claim
27 words
A composition according to claim 2 in which the comonomer is present in the monomer mixture in an amount above 40% by weight to 80% by weight.
Claim 11
Dependent Claim
16 words
A composition according to claim 9 in which the comonomer contains at least three fluorine atoms.
Claim 12
Dependent Claim
32 words
A composition according to claim 9 in which the comonomer is selected from hexafluoroisopropyl methacrylate, trifluoroethyl methacrylate, pentafluorostyrene, vinyl ethyl ketone, vinyl ethyl ether, vinyl iodide, vinyl bromide, methacryloxy-methylpentamethyl siloxane and 1,3-bis-(methacryloxymethyl)-disiloxane.
Claim 13
Independent Claim
102 words
A method of forming a suspension of polymeric beads having a density less than 1.15 g/cc or greater than 1.30 g/cc and an average diameter below 5 microns comprising the steps of: forming an ethylenically unsaturated monomer mixture consisting essentially of at least 10% by weight first ethylenically unsaturated monomer containing at least one substituent selected from hydroxyl, carboxyl or amino, at least 25% by weight of a second ethylenically unsaturated comonomer having a density differing from the first monomer by at least 15%, and 1-20% of a polyunsaturated cross-linking agent; and addition polymerizing the mixture to form said suspension of beads.
Claim 14
Independent Claim
102 words
A method of forming a suspension of polymeric beads having a density less than 1.15 g/cc or greater than 1.30 g/cc and an average diameter below 5 microns comprising the steps of: forming an ethylenically unsaturated monomer mixture consisting essentially of at least 10% by weight first ethylenically unsaturated monomer containing at least one substituent selected from hydroxyl, carboxyl or amino, at least 25% by weight of a second ethylenically unsaturated comonomer having a density differing from the first monomer by at least 15%, and 1-20% of a polyunsaturated cross-linking agent; and addition polymerizing the mixture to form said suspension of beads.
Claim 15
Dependent Claim
105 words
A method according to claim 12 in which the first monomer is present in the mixture in an amount from 20 to 60% by weight and is selected from acrylamide, hydroxy-lower alkyl acrylates, amino-lower alkyl acrylates, acrylic acid or methacrylic acid, the cross-linking agent is present in an amount from 5-15% by weight and is selected from ethylene glycol dimethacrylate, divinyl benzene, trimethylol propane trimethacrylate, and N,N'-methylene-bis-acrylamide, and the comonomer is present in the mixture in an amount from 40-80% by weight and is selected from hexafluoroisopropyl methacrylate, trifluoroethyl methacrylate, pentafluorostyrene, vinyl ethyl ketone, vinyl ethyl ether, vinyl iodide, vinyl bromide, methacryloxy-methylpentamethyl siloxane and 1,3-bis-(methacryloxymethyl)-disiloxane.
Claim 16
Dependent Claim
34 words
A method according to claim 13 in which the polymerization is conducted by aqueous emulsion polymerization of said monomer mixture and the total monomer content is from 3-40% by weight of the polymerization composition.
Claim 17
Dependent Claim
26 words
A composition according to claim 9 in which the comonomer is selected from vinyl fluorides, vinyl ketones, vinyl ethers, vinyl iodides, vinyl bromides, and vinyl siloxanes.
Claim 18
Dependent Claim
19 words
A protein specific reagent comprising the bead composition of claim 1 covalently bonded to a conjugate of said protein.
References Cited (Backward Citations)
US3957741A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-07-11 | 1981-01-10 | 1981-07-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-07-11 | 1985-01-10 | 1985-07-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-07-11 | 1989-01-10 | 1989-07-12 | $7700.00 | Window Closed / Lapsed |