Irori

Hybritech Incorporated

Discovery Partners International, Inc.

Other

Eli Lilly and Company

Nexus Biosystems, Inc.

Irori Technologies, Inc.

Gary S David

Michael P Nova

Andrew E Senyei

Zahra Parandoosh

Xiao-Yi Xiao

Hanan Potash

Chanfeng Zhao

Yozo Satoda

Howard E Greene

John E Lillig

Claude F Meares

Anthony W Czarnik

Michele C Smith

Gordon W Hudson

Leslie D Anderson

Willem P Stemmer

Mary S Kasher

Susan M Hochschwender

James A Cook

Robert Neeper

In a multiplexed assay, each molecule of a plurality of molecules is attached to a support matrix with a substrate adapted for attachment and/or synthesis of molecules and an integrally-formed memory device with an optically-encoded identifier to uniquely identify the molecule attached to the substrate. The molecules are exposed to one or more processing conditions then placed within the path of an optical detector adapted to read the optically-encoded identifier and measure biochemical processes on each support matrix. The support matrices may besingulated to be read by the optical detector one at a time.

Multiplexed assay using encoded solid support matrices

Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The data storage units are non-volatile antifuse memories or volatile memories, such as EEPROMS, DRAMS or flash memory. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided. The combinations have a multiplicity of applications, including combinatorial chemistry, isolation and purification of target macromolecules, capture and detection of macromolecules for analytical purposes, selective removal of contaminants, enzymatic catalysis, cell sorting, drug delivery, chemical modification and other uses. Methods for electronically tagging molecules, biological particles and matrix support materials, immunoassays, receptor binding assays, scintillation proximity assays, non-radioactive proximity assays, and other methods are also provided.

Multiplexed assays using encoded solid supports

Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are non-volatile antifuse memories or volatile memories, such as EEPROMS, DRAMS or flash memory. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided. The combinations have a multiplicity of applications, including combinatorial chemistry, isolation and purification of target macromolecules, capture and detection of macromolecules for analytical purposes, selective removal of contaminants, enzymatic catalysis, cell sorting, drug delivery, chemical modification and other uses. Methods for electronically tagging molecules, biological particles and matrix support materials, immunoassays, receptor binding assays, and other methods are also provided.

Remotely programmable matrices with memories

Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are preferably non-volatile antifuse memories. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided. The combinations have a multiplicity of applications, including combinatorial chemistry, isolation and purification of target macromolecules, capture and detection of macromolecules for analytical purposes, selective removal of contaminants, enzymatic catalysis, chemical modification and other uses. Methods for electronically tagging molecules are biological particles and matrix support materials and immunoassays and and other methods are also provided.

Combinations, called matrices with memories, of matrix materials that are encoded with an optically readable code are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The memories include electronic and optical storage media and also include optical memories, such as bar codes and other machine-readable codes. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided. The combinations have a multiplicity of applications, including combinatorial chemistry, isolation and purification of target macromolecules, capture and detection of macromolecules for analytical purposes, selective removal of contaminants, enzymatic catalysis, cell sorting, drug delivery, chemical modification and other uses. Methods for tagging molecules, biological particles and matrix support materials, immunoassays, receptor binding assays, scintillation proximity assays, non-radioactive proximity assays, and other methods are also provided.

Method for tagging and screening molecules

Methods for irradiation induced graft polymerization of a monomers, such as styrenes, onto fluoropolymers are provided. The methods, which involve either the use of acids, preferably mineral acids, or creating a rough surface on the fluoropolymer, provide higher levels of grafting of the copolymer than grafting in the absence of the acid or of the rough surface on the fluoropolymer. Also provided are grafted copolymers produced by the methods. Methods for increasing the performance of solid phase assays, such as scintillation proximity assays, are also provided.

Radiation-grafted solid supports for chemical synthesis

Remotely programmable matrices with memories and uses thereof

Matrices with memories and uses thereof

Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are preferably non-volatile antifuse memories. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided. The combinations have a multiplicity of applications, including combinatorial chemistry, isolation and purification of target macromolecules, capture and detection of macromolecules for analytical purposes, selective removal of contaminants, enzymatic catalysis, chemical modification and other uses.

A chelating agent is covalently bonded to a biologically active molecule such as an enzyme or antibody, the biologically active molecule is contacted with a support containing a bound transition metal ion whereby the metal ion is chelated by the chelating agent and the oxidation state of the metal ion is changed by treatment with an oxidizing or a reducing agent to provide a kinetically inert: oxidation state to immobilize the biologically active molecule on the support. The transition metal ion is preferably Co(II), Cr(II) or Ru(III) and the oxidation state of the metal ion is changed to Co(III), Cr(III) or Ru(II), respectively. The chelating agent can be iminodiacetic acid, nitrilotriacetic acid, terpyridine, bipyridine, triethylenetetraamine, biethylenetriamine, 1,4,7-triazacyclonane or a chelating peptide. Certain chelating agents can immobilize more than one biologically active molecule at a metal ion site on the support. The immobilized biologically active molecules can be used in affinity chromatography or in assay systems.

Immobilization of biologically active molecules by changing the

Monoclonal Antibodies which are specific for a complex of a chelating agent and a metallic ion are described. The antibody has an association constant (K.sub.a) for the complex which is at least about ten times greater than the K.sub.a for the chelating agent alone or its complex with another metal.

Monoclonal antibodies against metal chelates

'Two-site' or 'sandwich' immunometric assay techniques for determination of the presence and/or concentration of antigenic substances in fluids using monoclonal antibodies are described and compared to conventional assays using polyclonal antibodies. Also described are inhibition assays using complexes of antigens with a monoclonal antibody.

Immunometric assays using monoclonal antibodies

'Two-site' or 'sandwich' immunometric assay techniques for determination of the presence and/or concentration of antigenic substances in fluids using monoclonal antibodies. One monoclonal antibody is presented in a soluble labeled form and a second monoclonal antibody is presented bound to a solid carrier; the soluble and bound monoclonal antibodies may be the products of either the same or different cell lines. Each monoclonal antibody has an affinity for the antigenic substances of at least about 10.sup.8 liters/mole.

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La Jolla, CA, United States of America

Gary S David