Abbott Laboratories Corporation

Spectrx, Inc.

Mark R Pope

Neil W Loomis

Timothy P Henning

Thomas G Schapira

Tung-Ming Huang

Peter M Bojan

Robert G Hiltibran

Sie Ting Wong

Eric B Shain

Michael G Lowery

Andrew J Muetterties

David Dean Cunningham

Qiaoqiao Ruan

Sergey Y Tetin

John J Kotlarik

John P Grace

Brian Joseph Tarkowski

M Felicia Bogdan

Daniel P Schmidt

Richard Haack

Pete M Bojan

Kristin M Noonan

Christopher Bieniarz

Jonathan Eppstein

Mark A Hayden

Peter J Tarcha

Andrew G Fischer

Anthony Scott Muerhoff

Jeffrey B Huff

Thomas P Leary

Douglas F Young

Xiaoxing Qiu

Joseph Larry Pezzaniti

Sophie Laurenson

Shelley R Holets-McCormack

John C Prostko

Pathik H Soni

Lyle Yarnell

Terry A Pry

Zhen Lin

Lei Qiao

Kevin M Knigge

Dustin House

Edna Prieto-Ballengee

Peter J Karabatsos

Kerry M Swift

Mary K Joseph

Andrew S Schapals

Patrick J Macdonald

Brenda Calfin

David R Mees

M Shawn Murphy

C Brent Putman

Daniel D Subotich

Stefan Hershberger

Brenda B Calfin

Andrew T Fischer

Edna M Prieto-Ballengee

Felicia Bogdan

Peter N Bojan

Thomas Leary

The disclosure provides methods of analyzing an analyte of interest in a biological sample using fluorescent agents and macroconjugates which comprise a core containing a cross-linked polymer or protein, tags, specific binding members or fragments thereof, and optionally carrier proteins. Also provided are methods of analyzing two or more analytes of interest in a biological sample in a single assay using microparticles and detection conjugates comprising different fluorophore labels, acquiring transmitted light and fluorescent images of the microparticles, and using a customized image analysis process to analyze the acquired images.

Direct detection of single molecules on microparticles

Methods, devices, and systems for analyte analysis using a nanopore are disclosed. The methods, devices, and systems utilize a first and a second binding member that each specifically bind to an analyte in a biological sample. The method further includes detecting and/or counting a cleavable tag attached to the second binding member and correlating the presence and/or the number of tags to presence and/or concentration of the analyte. Certain aspects of the methods do not involve a tag, rather the second binding member may be directly detected/quantitated. The detecting and/or counting may be performed by translocating the tag/second binding member through a nanopore. Devices and systems that are programmed to carry out the disclosed methods are also provided.

Devices and methods for sample analysis

The present invention involves apparatus and methods for use in collecting bodily fluids, such as interstitial fluids, from the epidermal layer of an animal. A preferred apparatus includes a pressure head and, optionally, a holder therefor for supplying a positive pressure to the head. The methods include the application of a positive pressure to the area surrounding an epidermal site from which stratum corneum has been breached, such as by laser ablation, to cause bodily fluids, such as interstitial fluids, to exude from the site and collecting the fluids exuding therefrom.

Apparatus and method for the collection of interstitial fluids

Fluid collection and monitoring device

The invention involves a method for focusing light comprising the steps of: projecting at least one pulse of light onto the surface of the skin of a patient; collecting at least a portion of the light that is reflected from the skin of the patient; projecting the collected, reflected light onto a detector; and adjusting the projection of the pulsed light onto the surface of the skin of the patient in such a manner that the signal projected onto the detector is optimized. When the light pulse is properly focused, e.g., when it is characterized by the best focus, it can be used to provide energy to form an opening in the skin of the patient. When more than one pulse of light is required to form an opening in the skin of the patient, aligning the light prior to each pulse will improve the efficiency of formation of the opening. In general, the method for aligning and focussing is the same as the method for focusing, with the difference being that aligning further includes steps for moving the spot of light formed by the light so that it strikes the surface of the skin at or near the position on the surface of the skin of the patient at which the previous spot of light struck the skin.

Removal of stratum corneum by means of light

Diagnostic assay for a sample of biological fluid

A method for increasing the permeability of the stratum corneum by means of a source of light, preferably a laser, more preferably a pulsed laser. By increasing the permeability of the stratum corneum, access to the interstitial fluid is achieved, thereby enabling measurement of analytes in the interstitial fluid. In one aspect, the method comprises the steps of:

A method for increasing the binding activity of specific binding members bound to a solid phase material, e.g., a particle, that has been sterically stabilized. This increase in binding activity is brought about by degrading a steric stabilizer on the surface of the solid phase material. The method involves both immobilizing a specific binding member on the surface of a solid phase material and degrading a steric stabilizer on the surface of that solid phase material. In the preferred embodiment, the method involves the immobilization of a specific binding member on the surface of the sterically stabilized solid phase material, with subsequent degradation of the steric stabilizer.

Method for improving the performance of an immunoreagent in an

A specific binding member such as an antigen or antibody is immobilized by covalent attachment to a solid phase such as a latex microparticle. The solid phase is reacted with a heterobifunctional or homobifunctional coupling agent to form a complex that is then reacted with a dithiol compound to form a thiolated solid phase. A specific binding member is reacted with the coupling agent to form a complex which is then reacted with the thiolated solid phase to link the specific binding member to the solid phase through thioethers. Alternatively, the dithiol compound may be reacted with the specific binding member/coupling agent complex to form a thiolated complex that is reacted with the solid phase/coupling agent complex. The coupling agent may contain a spacer. In another embodiment, the solid phase is reacted with a disulfide compound to form a complex and the complex is reacted with a reductant to form a thiolated solid phase which is reacted with a specific binding member/coupling agent complex. The immobilized specific binding member can be used in diagnostic binding assays, and it has increased sensitivity, specificity and stability, while requiring the use of less specific binding member.

Covalent attachment of specific binding members to a solid phase with

Novel pyrene-trisulfonate derivatives and the use thereof in a method for the determination of glycohydrolytic enzyme activity are provided. The method comprises the steps of (a) forming a test solution comprising a test sample containing the glycohydrolytic enzyme and a pyrene-trisulfonate derivative of the present invention, wherein the derivative is hydrolyzed by the glycohydrolytic enzyme to result in the formation of free 8-hydroxy-1,3,6-pyrene trisulfonate as a function of, and which can be correlated to, the amount of the glycohydrolytic enzyme present in the test sample, and (b) measuring and correlating either the intensity of fluorescence, or the optical density, of the test solution to the presence or amount of the glycohydrolytic enzyme in the test sample. A preferred pyrene-trisulfonate derivative is pyrene-1,3,6-trisulfonic acid) 8-.beta. -D-glucuronide for the determination of .beta.-D-glucuronidase for the diagnosis of periodontal disease.

Reagents and methods for the determination of glycohydrolytic enzymes

A high concentration of renaturing surfactants is added to protein systems in the presence of alkyl sulfate detergents to displace the detergent with respect to the interaction with the protein, thereby renaturing the protein and restoring its reactivity. The presence of higher quantities of detergent in the system results in smaller protein aggregates, and thus a higher reactivity and specificity as measured for the system in its entirety.

Method for renaturing proteins in the presence of alkyl sulfate

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Grayslake, IL, United States of America

Mark R Pope