US20060166376A1 - Compositions for use as a signal generation component and methods of using same - Google Patents

Compositions for use as a signal generation component and methods of using same Download PDF

Info

Publication number
US20060166376A1
US20060166376A1 US11/040,887 US4088705A US2006166376A1 US 20060166376 A1 US20060166376 A1 US 20060166376A1 US 4088705 A US4088705 A US 4088705A US 2006166376 A1 US2006166376 A1 US 2006166376A1
Authority
US
United States
Prior art keywords
composition
carrier
aminodextran
metal chelate
signal generation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/040,887
Other languages
English (en)
Inventor
Alan Craig
Zhu Teng
Richard Wright
Chengrong Wang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Siemens Healthcare Diagnostics Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to US11/040,887 priority Critical patent/US20060166376A1/en
Assigned to DADE BEHRING INC. reassignment DADE BEHRING INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CRAIG, ALAN R., TENG, ZHU, WRIGHT, RICHARD C., WANG, CHENGRONG
Priority to PT06718583T priority patent/PT1856529E/pt
Priority to JP2007552204A priority patent/JP4741607B2/ja
Priority to ES06718583T priority patent/ES2392730T3/es
Priority to EP06718583A priority patent/EP1856529B1/en
Priority to PCT/US2006/001529 priority patent/WO2006078618A2/en
Publication of US20060166376A1 publication Critical patent/US20060166376A1/en
Priority to US11/499,519 priority patent/US7691647B2/en
Assigned to SIEMENS HEALTHCARE DIAGNOSTICS INC. reassignment SIEMENS HEALTHCARE DIAGNOSTICS INC. MERGER (SEE DOCUMENT FOR DETAILS). Assignors: DADE BEHRING INC.
Priority to US12/555,734 priority patent/US20090325316A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/585—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex
    • G01N33/586—Liposomes, microcapsules or cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2458/00—Labels used in chemical analysis of biological material
    • G01N2458/40—Rare earth chelates
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/968—High energy substrates, e.g. fluorescent, chemiluminescent, radioactive

Definitions

  • the present invention relates generally to compositions useful as signal generation components in immunoassays.
  • the invention relates to compositions that simultaneously provide a strong signal as well as an enhanced specificity for the analytes of interest.
  • Immunoassay reagents have functionality that can be broken down into two broad components: signal generation (also known as amplification) functionality, and ligand binding functionality.
  • signal generation functionality is required for detection of ligand binding to analyte
  • ligand binding functionality is the specificity of the reagent for the analyte.
  • the ligand binding activity is accomplished by covalently attaching ligands to the particle surface.
  • Antibodies and small haptens of biological significance, such as thyroxin, are examples of common ligands.
  • Flourescent and chemiluminescent compositions have been widely used in signal generation components of immunoassays.
  • a typical signal generation component includes a carrier, such as a latex particle, dyed with a flurosecent or chemiluminescent composition.
  • metal chelates have been widely used as fluroscent and chemiluminescent dyes because of their generally large stokes' shift, sharp emission peak and long emission wavelength.
  • the metal chelates are a complex formed of a metal, such as europium, samarium, or terbium, and ligands such as thiophenetrifluorobutanedione (TTA), napthyltriflurobutanedione (NTA), and 4, 7-diphenyl-1,10-phenathroline (DPP) trioctyl phosphine oxide (TOPO), triphenyl phosphine oxide (TPPO).
  • TTA thiophenetrifluorobutanedione
  • NDA napthyltriflurobutanedione
  • DPP 7-diphenyl-1,10-phenathroline
  • TOPO trioctyl phosphine oxide
  • TPPO triphenyl phosphine oxide
  • Some commonly used metal chelates include Eu(TTA) 3 DPP and Eu(NTA) 3 DPP.
  • Dyed carriers that are used to make assay reagents must have both the capability to provide signal generation, and the chemical functionality for covalent attachment of ligands.
  • the process used to attach the ligands can be critical to the quality of the specificity of the ligand binding functionality.
  • the specificity of the ligands can be compromised in several ways by inappropriate choices of attachment chemistry. For example, if passive adsorption of the ligands occurs simultaneously with covalent attachment, the passively adsorbed ligands may come off of the carrier during the assay. The resulting free ligand will interfere with the assay and reduce its sensitivity. Another problem that can occur is the non-specific binding of the reagent to the other carrier, which leads to elevation of the immunoassay signal in the absence of analyte.
  • Ligands are often attached to polystyrene particles through carboxy groups that are attached directly to the surface of the particles. This approach can have both of the problems described above.
  • the passive adsorption and nonspecific binding problems can be avoided by introducing one or more layers of immobilized hydrogel polymers, such as an aminodextran, between the polystyrene particles and the ligands. It is important for elimination of adsorption and nonspecific binding to have a continuous layer of these hydrogel polymers.
  • the coating of particles that are dyed with conventional dyes such as Eu(TTA) 3 DPP or Eu(NTA) 3 DPP typically result in coating densities of aminodextran that are significantly less than optimal for preventing non-specific binding.
  • the coupling density of the aminodextran is typically reduced by 40-50% from its maximum when these dyes are added at the optimum level for the chemiluminescent response of the reagent.
  • Lower levels of dye give compositions that interfere less with the aminodextran coating process, but reducing the dye content also reduces the chemiluminescence necessary for a strong signal.
  • compositions of the present invention provide signal generation components having an optimal balance between the reduction of non-specific binding while allowing an improved response signal.
  • a composition suitable for use as a signal generation component in an immunoassay includes a carrier having a coating of an aminodextran and dyed with a metal chelate.
  • the metal chelate is present in the amount of at least 0.065 ⁇ M per milligram of carrier, and the average aminodextran coating density is at least about 45 ⁇ g per milligram of carrier.
  • a composition according to another aspect of the invention includes a carrier coated with an aminodextran and with a complex incorporated therein having the formula: M (L1) x (L2) y ,
  • M is a metal selected from the group consisting of europium, terbium, dysprosium, samarium, osmium and ruthenium;
  • L1 is a ligand selected from the group consisting of DPP, TOPO, and TPPO;
  • a method of detecting the presence or amount of an analyte in a test sample suspected of containing the analyte comprises performing an immunoassay using the compositions of the present invention as a signal generating component.
  • FIG. 1 is a schematic illustrating the synthesis of one embodiment of a metal chelate according to the present invention.
  • FIG. 2 is a schematic illustrating the synthesis of another embodiment of a metal chelate according to the present invention.
  • FIG. 3 is a graphical representation of aminodextran concentration and response signal as functions of metal concentration for a prior art composition.
  • FIG. 4 is a graphical representation of aminodextran concentration and response signal as functions of metal concentration for compositions according to the present invention.
  • compositions of the present invention are useful as signal generation components in immunoassays.
  • the compositions generally include a carrier coated with an aminodextran and have a metal chelate incorporated therein.
  • the compositions provide strong response signals which allows for quantitative determinations of analytes of interest, while reducing errors caused by non-specific binding.
  • Carriers suitable for the present invention include solid phase materials, typically a support or surface, that can have any one of a number of shapes, such as strip, sheet, rod, plate, well, tube, particle or bead.
  • the material is usually of an organic or inorganic, swellable or non-swellable, porous or non-porous, magnetic or non-magnetic, water-insoluble material.
  • the surface can be hydrophilic or capable of being rendered hydrophilic.
  • the solid support includes inorganic powders such as silica, magnesium sulfate, and alumina; natural polymeric materials, particularly cellulosic materials and materials derived from cellulose, such as fiber containing papers, e.g., filter paper, chromatographic paper, etc.; synthetic or modified naturally occurring polymers, such as nitrocellulose, cellulose acetate, polyvinylchloride, polyacrylamide, crosslinked dextran, agarose, polyacrylate, polyethylene, polypropylene, poly(4-methylbutene), polystyrene, polymethacrylate, polyethyleneterephthalate, nylon, polyvinylbutyrate, etc.; either used by themselves or in conjunction with other materials; glass available as Bioglass, ceramics, magnetic materials, metals, and the like. Natural or synthetic assemblies such as liposomes, phospholipid vesicles, and cells can also be employed.
  • natural polymeric materials particularly cellulosic materials and materials derived from cellulose, such as fiber containing papers, e
  • the carrier is a particle.
  • “Particle”, as used herein, encompasses spheres, spheroids, beads and other shapes as well. Suitable particles are typically at least 20 nm and not more than about 20 ⁇ m, usually at least about 40 nm and less than 10 ⁇ m, preferably 0.1 to 10 ⁇ m, more preferably, 0.1 to 5 ⁇ m, and even more preferably 0.15 to 3 ⁇ m.
  • the particle may be organic or inorganic, swellable or non-swellable, porous or non-porous, having any density, but preferably of a density approximating water, generally from about 0.7 to about 1.5 g/ml, preferably suspendible in water, and composed of material that can be transparent, partially transparent, or opaque.
  • the particles may be core-and-shell particles, such as particles with a magnetic core and a hard shell coating of polymerized monomer(s).
  • the particles are preferably negative charged.
  • the particles are preferably solid, e.g., polymer particles, metal sols (particles comprised of a heavy metal such as, e.g., gold or silver), glass particles, silicon particles, magnetic particles, dye crystallites.
  • Latex means a particulate water-suspendible water-insoluble polymeric material.
  • the latex is frequently a substituted polyethylene such as: polystyrene-butadiene, polyacrylamide polystyrene, polystyrene with amino groups, poly-acrylic acid, polymethacrylic acid, acrylonitrile-butadiene, styrene copolymers, polyvinyl acetate-acrylate, polyvinyl pyrridine, vinyl-chloride acrylate copolymers, and the like.
  • Non-crosslinked polymers of styrene and carboxylated styrene or styrene functionalized with other active groups such as amino, hydroxyl, halo and the like are preferred. Frequently, copolymers of substituted styrenes with dienes such as butadiene will be used.
  • the carriers according to the present invention are coated with one or more layers layers of an aminodextran.
  • An aminodextran is a derivatized glucose polymer with amino groups having a molecular weight of about 10,000 to about 2,000,000, preferably about 500,000.
  • Methods of preparing aminodextrans and coating carriers are known in the art. Suitable methods are described in U.S. Pat. No. 5,707,877, columns 18-20, and U.S. Pat. No. 5,639,620, columns 21 and 22.
  • aminodextran is coated on the carrier by covalent attachment of the amino group of aminodextran to the surface carboxyl groups or other amine-reactive functional group of the carrier.
  • the aminodextran coating improves the specificity of the carrier in specific binding assays and therefore improves the sensitivity of immunoassays. It has been discovered that the metal chelate of the present invention unexpectedly allows for coating of carriers with aminodextran in the amount of at least about 45 ⁇ g per milligram of carrier in the presence of a dye concentration as high as at least 0.065 ⁇ M. According to one preferred embodiment of the present invention, the aminodextran coating is present in at least about 49 ⁇ g per milligram of carrier.
  • the carrier may be coated with a second layer comprising a polysaccharide, as described in U.S. Ser. No. 10/220,623.
  • the polysaccharide may be covalently coupled to the aminodextran layer by amine-reactive functional groups.
  • the second layer comprises dextran aldheyde.
  • a metal chelate is incorporated into the carrier through a known process, such as dyeing.
  • the metal chelate allows for a fluorescent or chemiluminescent signal to be detected.
  • the metal chelate is chosen such that relatively higher concentrations of the metal chelate do not interfere with the binding of the aminodextran coating to the carrier.
  • the metal chelate is present in the amount of at least 0.065 ⁇ M per milligram of carrier, while the aminodextran average coating density is at least about 45 ⁇ g per milligram of carrier.
  • the metal chelate is present in the amount of at least 0.065 ⁇ M and less than about 0.150 ⁇ M per milligram of carrier, more preferably about 0.079 ⁇ M to about 0.150 ⁇ M per milligram of carrier, and more preferably about 0.087 ⁇ M per milligram of carrier. In another embodiment of the invention, the metal chelate is present in the amount of about 0.110 ⁇ M to about 135 ⁇ M. These concentrations of metal chelate and aminodextran have been found to provide a proper balance of response signal and component specificity for the analyte of interest.
  • the metal chelate has the general formula M (L1) x (L2) y
  • M is a metal selected from the group consisting of europium, terbium, dysprosium, samarium, osmium and ruthenium;
  • L1 is a ligand selected from the group consisting of DPP, TOPO, and TPPO;
  • L2 comprises a ligand having the formula wherein R is one or more substituents, each substituent comprising an electron donating group;
  • n 2 ⁇ 10
  • Suitable electron donating groups are those that make available extra negative charge to the perfluoralkyl groups.
  • the electron donating group R is selected from the group consisting of C 1 to C 6 alkyls, dialkylamines, ethers, thioethers, and aryl groups.
  • the metal chelates of the present invention are effective in allowing optimized amounts of amindoextran to coat the carrier because the metal chelates provide an unexpectedly stable complex relative to prior metal chelate dyes.
  • the stability of the complex reduces the amount of the free metal, which is believed to inhibit the attachment of the aminodextran to the carrier.
  • electron donating groups R further add to the stability of the complex by making available additional negative charge to the perfluoroalkyl groups of the ligands, thereby improving the ability of the perfluoralkyl group to bind to the metal in the complex.
  • M is europium and the carrier is a latex particle.
  • L2 is selected from among the following formulas:
  • the ligands L2 are 2-(1′,1′,1′,2′,2′,3′,3′-heptafluoro-4′,6′-hexanedion-6′-yl)-naphthylene (NHA) and 4, 4′-bis (1′′,1′′,1′′,2′′,2′′,3′′, 3′′-heptafluroro-4′′,6′′-hexanedion-6′′-yl)-o-terphenyl (BHHT).
  • the metal chelate comprises Eu(NHA) 3 DPP and Eu(BHHT) 2 DPP.
  • the metal chelates can be prepared by combining the metal chloride with the desired ratio of metal ligand molecules in an organic solvent and sufficient base to take up the released hydrochloric acid. Suitable syntheses are illustrated in FIGS. 1-2 , respectively.
  • the metal chelate dyes of the present invention have been found to allow for a higher density of aminodextran coating at relatively higher concentrations of the metal chelate dyes when compared to conventional dyes, as demonstrated in the Comparative Examples below.
  • the metal chelates of the present invention generally will allow an aminodextran coating at about 45 to about 55 ⁇ g per mg beads compared to about 23 to about 35 ⁇ g per mg of bead for the conventional dyes.
  • the dyes of the present invention can be present in amounts sufficient to give strong response signals as part of a signal generation component in a specific binding assay, while allowing the carrier to be coated with an aminodextran in an amount sufficient to reduce the amount of non-specific binding.
  • compositions of the present invention are suitable for use as a signal generation component in specific binding assays.
  • the compositions are suitable for any immunoassay in which a signal is measured in response to ligand binding to an analyte.
  • Those skilled in the art will readily appreciate the compositions have wide utility in a number of assay formats.
  • the signal generating component is used to perform Luminescent Oxygen Channeling Immunoassay (LOCITM) as described in EP-A2-0 515 194.
  • LOCITM Luminescent Oxygen Channeling Immunoassay
  • at least one specific binding partner is bound to a carrier according to the present invention.
  • a medium suspected of containing an analyte is treated under conditions such the analyte affects the amount of a sensitizer capable in its excited state of generating singlet oxygen and a chemiluminescent compound that can come into close proximity such that singlet oxygen generated by said photosensitizer can activate said chemiluminescent compound, which subsequently produces light, and measuring the light, the amount thereof being related to the amount of analyte in said medium.
  • the LOCITM method includes the steps of: (A) combining either simultaneously or wholly or partially sequentially (i) a medium suspected of containing the analyte; (ii) a first specific binding partner associated with a sensitizer capable in its excited state of generating singlet oxygen; and (iii) a second specific binding partner associated with a composition comprising a chemiluminescent compound, which is a substance that undergoes a chemical reaction with singlet oxygen to form a metastabile intermediate species that can decompose with the simultaneous or subsequent emission of light; (B) allowing the formation of complexes comprising the first and the second specific binding partner, the complex formation brings the sensitizer into close proximity to the chemiluminescent compound, (C) activating the sensitizer to generate singlet oxygen; and measuring the amount of light emitted by the chemiluminescent compound, the light is directly or inversely proportional to the amount of analyte in the medium.
  • the carrier may be dyed both with a metal chelate and an oxygen acceptor.
  • the oxygen acceptor is a component that reacts with singlet oxygen to form a highly unstable product that rapidly decomposes into an excited state. The excess energy of the excited state is transferred to the dye by a Forster energy transfer that takes place in a few nanoseconds. The metal chelate dye then emits a photon of light that can be detected with a photon counter.
  • Suitable oxygen acceptors are disclosed in U.S. Pat. Nos. 5,578,498 and 5,811,311.
  • One particularly preferred oxygen acceptor is C-28 thioxene, which has the following formula:
  • a mixture of 100 mL 10% solution of carboxylated latex beads (from Seradyn), 138 ml 1-methoxy-2-propanol, 280 mL D.I. water and 10 mL of 0.1 M NaOH is placed in a three-necked flask equipped with a mechanical stirrer and a thermometer. The mixture is brought to 80° C. with stirring.
  • a separate solution is then prepared with a 2 g of C-28 thioxene and 2.7 g Eu(NHA) 3 DPP in 220 mL of 1-methoxy-2-propanol, and the solution is heated to 80° C. with stirring until dissolved.
  • the dye solution is then poured into the bead solution and stirred for 30 min.
  • the aminodextran coating is then applied as follows. 1 mL of the dyed beads ( ⁇ 20 mg/ml) is mixed with 20 mg/ml of hydroxypropylaminodextran (MW 500K) in 0.05M MES/pH 6.0 in the presence of 3.8 mg/ml EDAC. After incubating this mixture for 16 hours at room temperature, (in the dark) the beads were washed once with 2 ml of 0.05M MES/pH 6.0, then with 6 ml of 0.05M MES, 1.0M NaCl/pH 6.0. Finally the beads were resuspended in 1 ml of 0.05M MES/pH 6.0 to yield the coated beads. Washing was performed by centrifugation method (using Sorval RC-5B Plus centifruge or Ependorf centrifuge-5415 C) and pellets were resuspended by sonication (using Branson Sonifer-450).
  • the dextran aldehyde layer may then be added as follows. 1 ml of the 20 mg/ml dextran aldehyde in 0.05M MES is mixed with 1 ml of the aminodextran coated chemiluminescent beads in the presence of 2 mg/ml NaBH 3 CN. After incubating for 37° C. for 20 hours (in the dark), the beads were washed once with 4 ml and then with another 5 ml of MES buffer. The beads were resuspended in 0.5 ml of 0.05MES, 0.4% Tween-20/pH 6.0 to yield about 40 mg/ml of coated beads.
  • a first set of latex particles were dyed with Eu (NTA) 3 DPP and thioxene and coated with an aminodextran according to the methods described herein.
  • a second set of latex particles were dyed with Eu (NHA) 3 DPP and thioxene and coated with an aminodextran.
  • the aminodextran coating densities and the chemiluminesence were simultaneously measured at several concentrations of the metal chelate.
  • the aminodextran coating density was measured by a colorimetric test after being treated with anthrone and 80% sulfuric acid.
  • the chemiluminescence was measured as LOCI counts by a Envision-Alpha reader sold by Perkin-Elmer.
  • the data points for Eu (NTA) 3 DPP are tabulated in Table 1 and shown graphically with curve fitting in FIG. 3 .
  • the data points for Eu(NHA) 3 DPP are tabulated in Table 2 and, for concentrations up to 0.094, are shown graphically with curve fitting in FIG. 4 .
  • the aminodextran loading and the LOCI signal could not be simultaneously poised on a plateau for response with respect to composition.
  • the response signal does not begin to plateau until about 0.085 mmoles Eu/gram of beads.
  • the aminodextran coating concentration is only at 36 ug/mg of beads, and continues to decline with increasing europium concentrations.
  • the compound according to the present invention begins to plateau both in terms of aminodextran concentration and LOCI signal with as little as 0.065 um Eu/gram of beads.
  • the average aminodextran coating concentration is 49 ⁇ g/mg beads.
  • the concentration of aminodextran generally holds steady as the concentration of europium is increased.
  • Latex beads from Seradyn were dyed with 0.171 mmol of Europium dye and 0.303 mmol of C-28 thioxene per gram of bead for each of two conventional dyes, Eu(TTA) 3 DPP and Eu(NTA) 3 DPP and two dyes according to the present invention, Eu(BHHT) 2 DPP and Eu(NHA) 3 DPP.
  • the beads were then coated with aminodextran as described herein. The densities of the aminodextran was then determined, as well as the amplitude of its response signal. The data are tabulated on Table 3.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Production Of Liquid Hydrocarbon Mixture For Refining Petroleum (AREA)
  • Catalysts (AREA)
  • Inorganic Compounds Of Heavy Metals (AREA)
US11/040,887 2005-01-21 2005-01-21 Compositions for use as a signal generation component and methods of using same Abandoned US20060166376A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
US11/040,887 US20060166376A1 (en) 2005-01-21 2005-01-21 Compositions for use as a signal generation component and methods of using same
PCT/US2006/001529 WO2006078618A2 (en) 2005-01-21 2006-01-17 Compositions for use as a signal generation component and methods of using same
EP06718583A EP1856529B1 (en) 2005-01-21 2006-01-17 Compositions for use as a signal generation component and methods of using same
JP2007552204A JP4741607B2 (ja) 2005-01-21 2006-01-17 シグナル産生成分として使用する組成物及びこれを用いる方法
ES06718583T ES2392730T3 (es) 2005-01-21 2006-01-17 Composiciones para el uso como un componente de generación de señales y métodos par usar las mismas
PT06718583T PT1856529E (pt) 2005-01-21 2006-01-17 Composições para utilização como componente de geração de sinal e métodos de utilização das mesmas
US11/499,519 US7691647B2 (en) 2005-01-21 2006-08-04 Compositions for use as a signal generation component and methods of using same
US12/555,734 US20090325316A1 (en) 2005-01-21 2009-09-08 Compositions for use as a Signal Generation Component and Methods of Using Same

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US11/040,887 US20060166376A1 (en) 2005-01-21 2005-01-21 Compositions for use as a signal generation component and methods of using same

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US11/499,519 Division US7691647B2 (en) 2005-01-21 2006-08-04 Compositions for use as a signal generation component and methods of using same
US12/555,734 Continuation US20090325316A1 (en) 2005-01-21 2009-09-08 Compositions for use as a Signal Generation Component and Methods of Using Same

Publications (1)

Publication Number Publication Date
US20060166376A1 true US20060166376A1 (en) 2006-07-27

Family

ID=36692776

Family Applications (3)

Application Number Title Priority Date Filing Date
US11/040,887 Abandoned US20060166376A1 (en) 2005-01-21 2005-01-21 Compositions for use as a signal generation component and methods of using same
US11/499,519 Expired - Lifetime US7691647B2 (en) 2005-01-21 2006-08-04 Compositions for use as a signal generation component and methods of using same
US12/555,734 Abandoned US20090325316A1 (en) 2005-01-21 2009-09-08 Compositions for use as a Signal Generation Component and Methods of Using Same

Family Applications After (2)

Application Number Title Priority Date Filing Date
US11/499,519 Expired - Lifetime US7691647B2 (en) 2005-01-21 2006-08-04 Compositions for use as a signal generation component and methods of using same
US12/555,734 Abandoned US20090325316A1 (en) 2005-01-21 2009-09-08 Compositions for use as a Signal Generation Component and Methods of Using Same

Country Status (6)

Country Link
US (3) US20060166376A1 (enExample)
EP (1) EP1856529B1 (enExample)
JP (1) JP4741607B2 (enExample)
ES (1) ES2392730T3 (enExample)
PT (1) PT1856529E (enExample)
WO (1) WO2006078618A2 (enExample)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080261239A1 (en) * 2006-11-13 2008-10-23 Perkinelmer Las, Inc. Detecting molecular interactions
US20110091978A1 (en) * 2009-10-21 2011-04-21 Siemens Healthcare Diagnostics Inc. Stabilization of signal generation in particles used in assays
WO2012009721A1 (en) 2010-07-16 2012-01-19 Elitech Holding B.V. Orthogonal nucleic acid affinity pairs

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8084215B2 (en) 2008-04-29 2011-12-27 Psychemedics Corporation Non-proteolytic method for the determination of analytes in keratinized structures
CN102077094B (zh) 2008-04-29 2016-03-09 赛凯米迪克斯股份有限公司 固相多分析物测试
US9347947B2 (en) 2009-03-12 2016-05-24 Siemens Healthcare Diagnostics Inc. Immunoassays employing non-particulate chemiluminescent reagent
EP2230515B1 (en) * 2009-03-16 2014-12-17 Agilent Technologies, Inc. Passivation of surfaces after ligand coupling
BR112014032907A2 (pt) 2012-06-28 2017-06-27 Psychemedics Corp detecção de analitos em amostras de lavagem de cabelo

Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4220450A (en) * 1978-04-05 1980-09-02 Syva Company Chemically induced fluorescence immunoassay
US4283382A (en) * 1977-12-28 1981-08-11 Eastman Kodak Company Fluorescent labels comprising rare earth chelates
US4565790A (en) * 1981-04-30 1986-01-21 Wallac Oy Method for fluorescence spectroscopic determination of a biologically active substance
US4587223A (en) * 1982-09-13 1986-05-06 Wallac Oy Method for quantitative determination of a biospecific affinity reaction
US4637988A (en) * 1981-07-01 1987-01-20 Eastman Kodak Company Fluorescent labels for immunoassay
US4925804A (en) * 1986-06-17 1990-05-15 Baxter International Inc. Interligand metal transfer assay
US4978625A (en) * 1987-10-19 1990-12-18 Becton, Dickinson And Company Fluorescence immunoassay using water insoluble dyes
US5316909A (en) * 1991-03-15 1994-05-31 Wallac Oy Method for increasing fluorescence
US5578498A (en) * 1991-05-22 1996-11-26 Behringwerke Ag Metal chelate containing compositions for use in chemiluminescent assays
US5639620A (en) * 1990-10-31 1997-06-17 Coulter Corporation Polymeric particles having a biodegradable gelatin or aminodextran coating and process for making same
US5707877A (en) * 1990-10-31 1998-01-13 Coulter Corporation Biodegradable gelatin-aminodextran particle coatings of and processes for making same
US5709994A (en) * 1992-07-31 1998-01-20 Syntex (U.S.A.) Inc. Photoactivatable chemiluminescent matrices
US6080839A (en) * 1998-06-25 2000-06-27 Wallac Oy Labeling reactants and their use
US6165729A (en) * 1986-04-30 2000-12-26 Hyperion Catalysis International, Inc. Electrochemiluminescent reaction utilizing amine-derived reductant
US20010055763A1 (en) * 1998-12-24 2001-12-27 Sharat Singh Individually addressable solid surfaces for multiplexed operations
US20010055776A1 (en) * 2000-02-11 2001-12-27 Dale Greenwalt High throughput cell-based assay kits
US6339172B1 (en) * 1998-04-28 2002-01-15 Kazuko Matsumoto Assay of substance in biological sample using labeled probe
US6399397B1 (en) * 1992-09-14 2002-06-04 Sri International Up-converting reporters for biological and other assays using laser excitation techniques
US20020150929A1 (en) * 2000-12-08 2002-10-17 Waseda University And Riken Detecting reagent for double-stranded nucleic acid and double-stranded nucleic acid detecting method
US20030133972A1 (en) * 2000-10-11 2003-07-17 Targesome, Inc. Targeted multivalent macromolecules
US20040082768A1 (en) * 2002-10-25 2004-04-29 Yerramilli Murthy Metal chelates and methods of using them for time-resolved fluorescence

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU657134B2 (en) 1991-05-22 1995-03-02 Dade Behring Marburg Gmbh Assay methods utilizing induced luminescence
US6389318B1 (en) * 1998-07-06 2002-05-14 Abiomed, Inc. Magnetic shield for primary coil of transcutaneous energy transfer device
JP3497092B2 (ja) * 1998-07-23 2004-02-16 名古屋大学長 プラズマ密度情報測定方法、および測定に用いられるプローブ、並びにプラズマ密度情報測定装置
CA2400993C (en) * 2000-03-06 2011-06-07 Dade Behring Marburg Gmbh Carriers coated with polysaccharides, their preparation and use
US6339397B1 (en) * 2000-06-01 2002-01-15 Lat-Lon, Llc Portable self-contained tracking unit and GPS tracking system
EP1409735A4 (en) 2001-06-25 2005-10-05 Georgia Tech Res Inst DOUBLE-RESONANCE ENERGY TRANSFER NUCLEIC PROBES
US20070106674A1 (en) * 2005-11-10 2007-05-10 Purusharth Agrawal Field sales process facilitation systems and methods

Patent Citations (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4283382A (en) * 1977-12-28 1981-08-11 Eastman Kodak Company Fluorescent labels comprising rare earth chelates
US4220450A (en) * 1978-04-05 1980-09-02 Syva Company Chemically induced fluorescence immunoassay
US4565790A (en) * 1981-04-30 1986-01-21 Wallac Oy Method for fluorescence spectroscopic determination of a biologically active substance
US4637988A (en) * 1981-07-01 1987-01-20 Eastman Kodak Company Fluorescent labels for immunoassay
US4587223A (en) * 1982-09-13 1986-05-06 Wallac Oy Method for quantitative determination of a biospecific affinity reaction
US6165729A (en) * 1986-04-30 2000-12-26 Hyperion Catalysis International, Inc. Electrochemiluminescent reaction utilizing amine-derived reductant
US4925804A (en) * 1986-06-17 1990-05-15 Baxter International Inc. Interligand metal transfer assay
US4978625A (en) * 1987-10-19 1990-12-18 Becton, Dickinson And Company Fluorescence immunoassay using water insoluble dyes
US5707877A (en) * 1990-10-31 1998-01-13 Coulter Corporation Biodegradable gelatin-aminodextran particle coatings of and processes for making same
US5639620A (en) * 1990-10-31 1997-06-17 Coulter Corporation Polymeric particles having a biodegradable gelatin or aminodextran coating and process for making same
US5316909A (en) * 1991-03-15 1994-05-31 Wallac Oy Method for increasing fluorescence
US5578498A (en) * 1991-05-22 1996-11-26 Behringwerke Ag Metal chelate containing compositions for use in chemiluminescent assays
US5811311A (en) * 1991-05-22 1998-09-22 Dade Behring Marburg Gmbh Metal chelate containing compositions for use in chemiluminescent assays
US5709994A (en) * 1992-07-31 1998-01-20 Syntex (U.S.A.) Inc. Photoactivatable chemiluminescent matrices
US6399397B1 (en) * 1992-09-14 2002-06-04 Sri International Up-converting reporters for biological and other assays using laser excitation techniques
US6339172B1 (en) * 1998-04-28 2002-01-15 Kazuko Matsumoto Assay of substance in biological sample using labeled probe
US20020106674A1 (en) * 1998-04-28 2002-08-08 Toyo Boseki Kabushiki Kaisha In situ assay of substance in biological sample using labeled probe
US6080839A (en) * 1998-06-25 2000-06-27 Wallac Oy Labeling reactants and their use
US20010055763A1 (en) * 1998-12-24 2001-12-27 Sharat Singh Individually addressable solid surfaces for multiplexed operations
US20010055776A1 (en) * 2000-02-11 2001-12-27 Dale Greenwalt High throughput cell-based assay kits
US20030133972A1 (en) * 2000-10-11 2003-07-17 Targesome, Inc. Targeted multivalent macromolecules
US20020150929A1 (en) * 2000-12-08 2002-10-17 Waseda University And Riken Detecting reagent for double-stranded nucleic acid and double-stranded nucleic acid detecting method
US20040082768A1 (en) * 2002-10-25 2004-04-29 Yerramilli Murthy Metal chelates and methods of using them for time-resolved fluorescence

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080261239A1 (en) * 2006-11-13 2008-10-23 Perkinelmer Las, Inc. Detecting molecular interactions
US9146233B2 (en) * 2006-11-13 2015-09-29 Perkinelmer Health Sciences, Inc. Detecting molecular interactions by fluorescence resonance energy transfer on a solid-phase support
US20110091978A1 (en) * 2009-10-21 2011-04-21 Siemens Healthcare Diagnostics Inc. Stabilization of signal generation in particles used in assays
US8153442B2 (en) 2009-10-21 2012-04-10 Siemens Healthcare Diagnostics Inc. Stabilization of signal generation in particles used in assays
WO2012009721A1 (en) 2010-07-16 2012-01-19 Elitech Holding B.V. Orthogonal nucleic acid affinity pairs

Also Published As

Publication number Publication date
US20060270063A1 (en) 2006-11-30
WO2006078618A2 (en) 2006-07-27
US7691647B2 (en) 2010-04-06
EP1856529A2 (en) 2007-11-21
EP1856529B1 (en) 2012-07-25
US20090325316A1 (en) 2009-12-31
PT1856529E (pt) 2012-09-24
EP1856529A4 (en) 2010-07-07
WO2006078618A3 (en) 2006-11-16
JP2008528969A (ja) 2008-07-31
ES2392730T3 (es) 2012-12-13
JP4741607B2 (ja) 2011-08-03

Similar Documents

Publication Publication Date Title
US20090325316A1 (en) Compositions for use as a Signal Generation Component and Methods of Using Same
US4735907A (en) Stabilized fluorescent rare earth labels and labeled physiologically reactive species
US4719182A (en) Fluorescent labels and labeled species and their use in analytical elements and determinations
US4283382A (en) Fluorescent labels comprising rare earth chelates
CA2126447C (en) Improved membrane for chemiluminescent blotting applications
US5710006A (en) Reagents for specific binding assays
EP0002963B1 (en) Aqueous stabilized fluorescent labels, proteins labelled therewith and methods of use
US20150323541A1 (en) Methods and reagents for analyte detection
US4269938A (en) Assay of peroxidatively active materials
EP0070832A1 (en) Microencapsulated fluorescer composition, test kit and system for immunoassay
Xu et al. Multiple fluorescent labeling of silica nanoparticles with lanthanide chelates for highly sensitive time-resolved immunofluorometric assays
JP4060380B2 (ja) カチオン界面活性剤もしくはポリマー及び４′−ヒドロキシアセトアニリドを含有する化学ルミネセンス組成物、試験キット並びに分析方法におけるそれらの用途
CA1166133A (en) Chemical luminescence amplification substrate system for immuno chemistry
CA2157062C (en) Chemiluminescent reagent and assay using a substituted acetanilide for light generation
CN111504959A (zh) C肽稀土荧光微球试剂盒及其检测卡和制备方法
EP0693552B1 (en) Analytical element, composition and method using modified apo-horseradish peroxidase
CN115678540A (zh) 一种基于zif-8包覆的复合材料的制备方法及其应用
AU582341B2 (en) Assay for immobilized reporter groups
CN120441745B (zh) 一种aipe磷光微球及其制备方法和应用
CA1255213A (en) Assay for immobilized reporter groups
CN118671363A (zh) 一种rh血型基因检测试剂盒及其制备方法
CN118759174A (zh) 一种基于量子点荧光微球的试纸检测方法
JPH11512282A (ja) シグナル発生酵素としてバナジウムブロモペルオキシダーゼを使った特異的結合リガンドの測定用の分析要素および方法

Legal Events

Date Code Title Description
AS Assignment

Owner name: DADE BEHRING INC., ILLINOIS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:CRAIG, ALAN R.;TENG, ZHU;WRIGHT, RICHARD C.;AND OTHERS;REEL/FRAME:015871/0106;SIGNING DATES FROM 20050211 TO 20050224

AS Assignment

Owner name: SIEMENS HEALTHCARE DIAGNOSTICS INC., ILLINOIS

Free format text: MERGER;ASSIGNOR:DADE BEHRING INC.;REEL/FRAME:020690/0530

Effective date: 20071231

Owner name: SIEMENS HEALTHCARE DIAGNOSTICS INC.,ILLINOIS

Free format text: MERGER;ASSIGNOR:DADE BEHRING INC.;REEL/FRAME:020690/0530

Effective date: 20071231

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION