Becton Dickinson and Company Limited

Beckon, Dickson and Company

Helen V Hsieh

J Bruce Pitner

Jason E Gestwicki

James G Nadeau

C Preston Linn

Zachary A Pfieffer

Alexander George Lastovich

Robert E Pearson

James L Schram

Christian Sandmann

Steven Keith

Adam C Curry

Kristin Weidemaier

Andrea Liebmann-Vinson

Rajendra R Bhat

W William Stewart

Douglas Byron Sherman

Colleen M Nycz

Terry J Amiss

David J Wright

W Shannon Dillmore

William Shannon Dillmore

Adam Craig Curry

Kirstin Weidemaier

Disclosed herein are diagnostic assays using surface enhanced Raman spectroscopy (SERS)-active particles, including liquid-based assays; magnetic capture assays; microparticle-nanoparticle satellite structures for signal amplification in an assay; composite SERS-active particles useful for enhanced detection of targets; and sample tubes and processes for using the same.

Assays using surface-enhanced raman spectroscopy (SERS)-active particles

The invention is directed to compositions of mutated binding proteins containing reporter groups, analyte biosensor devices derived therefrom, and their use as analyte biosensors both in vitro and in vivo.

Binding proteins as biosensors

The invention is directed to compositions of mutated binding proteins containing thiol groups for coupling to sensor surfaces, analyte biosensor devices derived there from, and methods of their use as analyte biosensors both in vitro and in vivo.

Binding protein as biosensors

Methods for detection and analysis of allosteric receptor/ligand binding by changes in surface refractive index are provided. When analyzed by surface plasmon resonance, binding of such allosteric binding agents to their ligands may result in a negative deviation in the optical response (i.e., a decrease in resonance angle) or in an increase in the optical response (i.e., an increase in resonance angle) depending on the binding properties of the selected allosteric receptor. Other methods for analysis of surface refractive index are also useful in the invention. The methods of the invention are particularly useful for small ligands which would not be expected to produce detectable changes in refractive index because they do not add significant mass upon binding.

Detection of ligands by refractive surface methods

Detector nucleic acids are employed for detection of nucleic acid target sequences by fluorescence quenching mechanisms. The detector nucleic acid comprises at least two oligonucleotides and is partially single-stranded and partially double-stranded. One of the two dyes of a donor/acceptor dye pair is linked to the first oligonucleotide and the other is linked to a second oligonucleotide such that they are in close spatial proximity when the first and second oligonucleotides are base-paired and donor fluorescence is quenched. A single second oligonucleotide may be hybridized to the first oligonucleotide or multiple second oligonucleotides may be hybridized to the first oligonucleotide and to each other, forming a junction structure comprising multiple donor/acceptor dye pairs. The detector oligonucleotide retains its partially single-stranded and partially double-stranded conformation in the absence of target. In the presence of target, however, the second oligonucleotide(s) of the detector nucleic acid is/are completely or partially displaced from the first, increasing the distance between the donor and acceptor dyes and causing a change in fluorescence which may be detected as an indication of the presence of the target sequence.

Detection of nucleic acids by strand displacement

Detection of nucleic acids by fluorescence quenching

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Durham, NC, United States of America

Helen V Hsieh