Ciba Corning Diagnostics Corp.

Bayer Corporation

Chiron Diagnostics Corporation

Siemens Healthcare Diagnostics Gmbh

Bayer Healthcare LLC

Ciba-Geigy Ag

Charm Sciences, Inc.

Siemens Medical Solutions Diagnostic

Say-Jong Law

Qingping Jiang

Anand Natrajan

David J Sharpe

Uri Piran

Steve C Chang

Todd B Sells

Walter Fischer

John T Unger

Guohan Yang

Hartmut Schroeder

Elizabeth K Krodel

Hana Lukinsky

Roger S Cubicciotti

Stephen A Palmacci

Wen-Jee Wong

Jun Xi

Stanley E Charm

Marcus Baumann

Brian David Warner

Thomas Horn

Steven J Saul

Chariklia Sotiriou-Leventis

Ellen H Fiss

Adrian Waldner

John E Monahan

Rolf Hilfiker

Alex Alder

Donna M Ford

George Henry Parsons

Fritz Thommen

Paul Senn

Erika Schmidt

Christine A Vitkauskas

Carol K Klukas

Stephen M Tirrell

Constance R McCudden

John P Kilroy

Peter B Connolly

Chemiluminescent acridinium compounds are used in homogeneous assays to determine the concentration of an analyte in a sample without strong acid or strong base treatment. The chemiluminescent acridinium compounds include acridinium esters with electron donating functional groups at the C2 and/or C7 position on the acridinium nucleus to inhibit pseudo-base formation, or acridinium sulfonamides with or without electron donating functional groups at the C2 and/or C7 position on the acridinium nucleus.

Applications of acridinium compounds and derivatives in homogeneous assays

An antibody and immunogen for generating an antibody to nitrofuran and/or nitrofuran metabolite such as tissue or protein bound nitrofuran metabolites. Nitrofurans and and/or nitrofuran metabolites in a biological sample can be detected by contacting the sample with the antibodies to form a complex that can be detected. The antibodies may also be incorporated into test kits for the detection of nitrofuran and/or nitrofuran metabolites.

Method and antibodies for detecting nitrofuran

A method for the detection or quantitation of unlabeled target analyte in a biological sample, the method comprising labeling a target analyte for a biological sample suspected of containing unlabeled target analyte with an acridinium compound to form a labeled target analyte and providing the labeled target analyte to the biological sample, or providing the labeled target analyte to the biological sample, wherein the acridinium compound comprises an acridinium nucleus having an electron-donating substituent directly attached to the acridinium nucleus, with the electron-donating substituent attached at the Cposition. Chemiluminescent acridinium compounds useful in the method have emission maxima close to or in the near infrared (NIR) region (&#x3e;590 nm). These chemiluminescent acridinium compounds when used in conjunction with short wavelength-emitting acridinium esters (with emission maxima below 450 nm) can be highly useful labels for the simultaneous detection of multiple target analytes in a single assay.

Near infrared chemiluminescent acridinium compounds and uses thereof

A chemiluminescent substrate of a hydrolytic enzyme having the following general Formula I is disclosed, as follows:Lumi-M-P&#x2003;&#x2003;Formula Iwhere 'Lumi' is a chemiluminescent moiety capable of producing light (a) by itself, (b) with MP attached and (c) with M attached. Examples of Lumi include chemiluminescent acridinium compounds, benzacridinium compounds, quinolinium compounds, isoquinolinium compounds, phenanthridinium compounds, and lucigenin compounds, spiroacridan compounds, luminol compounds and isoluminol compounds. M is a multivalent heteroatom having at least one lone pair of electrons selected from oxygen, nitrogen and sulfur, directly attached to the light emitting moiety of Lumi at one end and to P at the other end. P is a group that can be readily removed by hydrolytic enzymes. An enzymatic reaction utilizing the above compound is the following: where HE is a hydrolytic enzyme. Lumi-M is a chemiluminescent product having physical and/or chemical properties different from those of Lumi-M-P.

Chemiluminescent acridinium compounds and analogues thereof as substrates of hydrolytic enzymes

A chemiluminescent substrate of a hydrolytic enzyme having the following general Formula I is disclosed, as follows:Lumi-M-PFormula Iwhere 'Lumi' is a chemiluminescent moiety capable of producing light (a) by itself, (b) with MP attached and (c) with M attached. Examples of Lumi include chemiluminescent acridinium compounds, benzacridinium compounds, quinolinium compounds, isoquinolinium compounds, phenanthridinium compounds, and lucigenin compounds, spiroacridan compounds, luminol compounds and isoluminol compounds. M is a multivalent heteroatom having at least one lone pair of electrons selected from oxygen, nitrogen and sulfur, directly attached to the light emitting moiety of Lumi at one end and to P at the other end. P is a group that can be readily removed by hydrolytic enzymes. An enzymatic reaction utilizing the above compound is the following: where HE is a hydrolytic enzyme. Lumi-M is a chemiluminescent product having physical and/or chemical properties different from those of Lumi-M-P.

A method for the detection or quantitation of an analyte in a biological sample is disclosed. The method comprises the steps of selecting a biological sample suspected of containing a target analyte and binding the target analyte in the sample to a binding partner conjugated to an acridinium compound, wherein the acridinium compound comprises an acridinium nucleus having an electron-donating substituent directly attached to the acridinium nucleus at the Cposition. Chemiluminescent acridinium compounds useful in the method have emission maxima close to or in the near infrared (NIR) region (&#x3e;590 nm). These chemiluminescent acridinium compounds when used in conjunction with short wavelength-emitting acridinium esters (with emission maxima below 450 nm) can be highly useful labels for the simultaneous detection of multiple target analytes in a single assay.

Measurement of hydride using chemiluminescent acridinium compounds and applications thereof

Highly hydrophilic non-nucleosidic tags with multiple labels are provided for use in nucleic acid probes. The tags are branched structures having a phosphodiester backbone, which have the advantages of a small dimensional size and high hydrophilicity. After the tag is labeled, its high negative charge and minimal size help to keep the carriers away from DNA or RNA molecules, due to repulsion between negative charges. Non-specific intercalation and steric hindrance are therefore minimized, and the hydrophobicity, if any of reporter molecules is reduced. The probes are used in place of conventionally labeled oligonucleotides for a variety of hybridization reactions.

Nucleic acid probes having highly hydrophilic non-nucleosidic tags with multiple labels, and uses thereof

Methods are provided for reducing background signals encountered in nucleic acid hybridization assays and other assays that involve hybridization of a labeled oligomer to its complement. The method is premised on the significant reduction of signal generation that occurs when a quenchable dye-labeled oligomer forms a hybrid complex. In addition, a method is provided for enhancing the detectable signal emitted from an amplification multimer hybridized to an oligomer probe to which a quenchable dye has been conjugated through a linker such that the emission from the dye is not quenched upon hybrid complex formation. Novel oligonucleotide probes are also provided that comprise an oligomer to which has been directly or indirectly through a linker a quenchable dye.

Oligonucleotide probes bearing quenchable fluorescent labels, and methods of use thereof

This application relates to long-wavelength acridinium compounds having electron-donating groups, which may either be: (a) Part of an extended conjugation system attached by appropriate functional groups to the acridinium nucleus, with coplanarity of the attached functional group and the acridone moiety during light emission (geometry requirement), said functional group consisting of at least one aromatic ring and one electron-donating atom or group with an extra pair of electrons which can readily delocalize into the extended &pgr; system to which the heteroatom is directly attached or built into, and establish stable extended resonance with the electron-withdrawing carbonyl moiety of the light emitting acridone. Such electron-donating atom or group that exists in the form of an anion has particularly strong effect to further the bathochromic shift of the emission wavelength; or (b) directly attached at one or more of positions C-2, C-4, C-5, or C-7 of the acridinium nucleus, of electron-donating atoms or groups having extra pair(s) of electrons. The electron-donating entities can be the same or different if more than one electron-donating entity is used. An electron-donating atom or group that exists in the form of an anion has particularly strong effect to further the bathochromic shift of the emission wavelength.

A new class of chemiluminescent acridinium or benzacridinium compounds is disclosed by virtue of forming an intramolecular energy transfer conjugate (ETC) between the acridinium or benzacridinium compound and a luminophore. A method of extending the emission wavelengths of acridinium or benzacridinium esters in order to further reduce or eliminate the emission spectral overlap between the parent polysubstituted aryl Acridinium Esters (DMAE) and Benzacridinium Esters (LEAE) is disclosed. The ETC's retain the unique desired properties of acridinium or benzacridinium compounds including complete light emission in very short period of time, monophasic emission spectrum, simplicity of triggering mechanism, ability of labeling the biological molecules of interest to form a tracer, and good stability. Additionally, the range of the emission spectrum of an acridinium or benzacridinium compound can now be shifted at will and at longer leap through the choice of a luminophore as the integral part of an ETC molecule. Disclosed are chemiluminescent labeled conjugates comprising an acridinium or benzacridinium moiety covalently attached to a luminophore via a spacer, said moiety further conjugated to a biological molecule of interest, wherein said spacer is of an appropriate length to allow the excited species generated from said moiety to transfer energy efficiently to said luminophore, resulting in the emission of light in the spectral region of said luminophore. Also disclosed are binding assays using said conjugates, test kits comprising said conjugates and methods of preparing the conjugates.

Chemiluminescent energy transfer conjugates and their uses as labels in

This invention is directed to novel nucleophilic polysubstituted aryl acridinium conjugates and the methods for preparation thereof. The novel nucleophilic polysubstituted aryl acridinium conjugates are useful in biological assays, including novel assays for the determination of Vitamin B.sub.12, folate, cortisol, estradiol, and thromboxane B.sub.2.

Nucleophilic polysubstituted aryl acridinium ester conjugates and

An assay method incorporating at least two different chemiluminescent compounds for detection and/or quantitation of at least two substances in a test sample is described. The synthesis of chemiluminescent reagents or conjugates for use in such methods as well as kits incorporating such reagents are also disclosed. The assays have particular application in the field of clinical diagnostics.

Long emission wavelength chemiluminescent compounds and their use in

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Westwood, MA, United States of America

Say-Jong Law