Sequenom, Inc.

Caprotec Bioanalytics Gmbh

Other

Boston University

Pharmaceuticals Corporation

Agena Biosciences, Inc.

Hubert Koster

Agena Bioscience, Inc.

Hubert Köster

Charles Cantor

Daniel P Little

Andreas Braun

Christian Jurinke

Maryanne J O'Donnell-Maloney

Dirk Johannes Van Den Boom

Daniel Paul Little

Franz Hillenkamp

Ping Yip

Andreas Ruppert

Liyan He

Norman Chiu

Ralf Wörl

Suhaib Mahmood Siddiqi

Subramanian Marappan

Cassandra L Smith

Dirk Van Den Boom

Charles Rodi

Dong-Jing Fu

Matthew Peter Grealish

Suhaib Siddigi

Yip Ping

Chester Frederick Hassman, Iii

Charlie Rodi

Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Automated systems for performing the methods also are provided.

Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions

Provided herein are substrates for matrix-assisted laser-desorption ionization (MALDI) mass spectrometric analysis. Each spot includes 3-hydroxypicolinic acid matrix and no analyte.

Matrix-assisted laser desorption ionization mass spectrometry substrates having low volume matrix array elements

Processes and methods for creating a database of genomic samples from healthy human donors, methods that use the database to identify and correlate polymorphic genetic markers and other markers with diseases and conditions are provided.

Methods for generating databases and databases for identifying polymorphic genetic markers

Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Each compound has the formula: wherein: Z is a trityl derivative; X, the reactivity function, covalently binds to amino acid side chains of proteins; Y, the selectivity function, modulates binding of X to the amino acid side chains in proteins such that X binds to fewer proteins when Y is present than in its absence; and Q permits separation or immobilization of the capture compound. Automated systems for performing the methods also are provided.

Capture Collections of capture compounds and collections thereof and methods using the compounds collections for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds in the collections are multifunctional reagents that provide for the separation and isolation of biomolecules in complex protein mixtures. In the collections, each and every compound in the collection, has the formula: Z is a trityl derivative, each of m and n independently is an integer that is 1 to 100; X, the reactivity function, covalently binds to amino acid side chains of biomolecules; Y, the selectivity function, modulates binding of X to the amino acid side chains in biomolecules such that X binds to fewer biomolecules when the selectivity moiety Y is present than in its absence; and Q permits separation or immobilization of capture compounds in the collection. Automated systems for performing the methods also are provided.

This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include DNA or RNA in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

Solid phase sequencing of biopolymers

Fast and highly accurate mass spectrometry-based processes for detecting particular nucleic acid molecules and mutations in the molecules are provided. In some embodiments, a process comprises: amplifying one or more target nucleic acid molecules from a biological sample; ionizing and volatilizing the amplified product; and analyzing a product by mass spectrometry to determine an observed molecular mass of the product.

Mass spectrometric methods for detecting mutations in a target nucleic acid

Provided are methods for detecting a target nucleic acid in a biological sample using RNA amplification. In an embodiment, provided is a method that comprises (a) amplifying a target nucleic acid, or portion thereof, using a primer comprising a sequence that is complementary to a polynucleotide sequence in the target nucleic acid, or a complement thereof, and a sequence that encodes an RNA polymerase promoter; (b) synthesizing RNA using an RNA polymerase that recognizes the promoter; and (c) detecting the presence or absence of the resulting RNA using mass spectrometry thereby detecting the presence or absence of the target nucleic acid in the biological sample.

DNA diagnostics based on mass spectrometry

Provided herein in certain embodiments are processes that generally include the following steps: amplifying a target nucleic acid molecule; ionizing and volatilizing the amplification product and analyzing the ionized and volatilized product by mass spectrometry. In some embodiments the amplification product is a natural nucleic acid and detection of the target nucleotide sequence by mass spectrometry indicates the presence of the target nucleotide sequence in the biological sample.

The invention provides methods for dispensing tools that can be employed to generate multi-element arrays of sample material on a substrate surface. The substrates surfaces can be flat or geometrically altered to include wells of receiving material. The tool can dispense a spot of fluid to a substrate surface by spraying the fluid from the pin, contacting the substrate surface or forming a drop that touches against the substrate surface. The tool can form an array of sample material by dispensing sample material in a series of steps, while moving the pin to different locations above the substrate surface to form the sample array. The invention then passes the prepared sample arrays to a plate assembly that disposes the sample arrays for analysis by mass spectrometry. To this end, a mass spectrometer is provided that generates a set of spectra signal which can be understood as indicative of the composition of the sample material under analysis.

Systems and methods for preparing and analyzing low volume analyte array elements

Methods for dispensing tools that can be employed to generate multi-element arrays of sample material on a substrate surface. The resulting substrates are also provided. The substrates surfaces can be flat or geometrically altered to include wells of receiving material. The tool can dispense a spot of fluid to a substrate surface by spraying the fluid from the pin, contacting the substrate surface or forming a drop that touches against the substrate surface. The tool can form an array of sample material by dispensing sample material in a series of steps, while moving the pin to different locations above the substrate surface to form the sample array. The prepared sample arrays are passed to a plate assembly that disposes the sample arrays for analysis by mass spectrometry. To this end, a mass spectrometer is provided that generates a set of spectra signals that are indicative of the composition of the sample material under analysis.

Fast and highly accurate mass spectrometry-based processes for detecting a particular nucleic acid sequence in a biological sample are provided. Depending on the sequence to be detected, the processes can be used, for example, to diagnose a genetic disease or chromosomal abnormality; a predisposition to a disease or condition, infection by a pathogenic organism, or for determining identity or heredity.

Multifunctional liquid phase carriers (LPCs) and methods of using LPCs for the preparation of biopolymers are provided. The LPCs are highly symmetrical compounds that possess more than two points of attachment for biopolymer synthesis. The LPCs have the formula Sp(X), where Sp is a highly symmetrical moiety such that all Xgroups are equivalent. Xis a functional group that is suitable for biopolymer synthesis, including OH, SH, NH, COOH and the like. Biopolymers that may be produced using the methods provided include oligonucleotides, peptides, protein nucleic acids (PNAs) and oligosaccharides. Analogs of the biopolymers may also be prepared using the methods.

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La Jolla, CA, United States of America

Hubert Köster