Sequenom, Inc.

Other

Hubert K&ouml;ster

Daniel P Little

Charles Cantor

Andreas Braun

David M Lough

G Scott Higgins

Thomas Becker

Christian Jurinke

Dirk Van Den Boom

Dong-Jing Fu

Young Tae Kim

Cassandra L Smith

Jhobe Steadman

Ping Yip

Richard A MacDonald

Maryanne J O'Donnell-Maloney

Dirk Reuter

Brigitte Darnhofer-Demar

Guobing Xiang

Maryanne J Little

Young-Soo Kwon

Changwon Kang

Scott Higgins

Kai Tang

Carsten W Siegert

Processes and kits for immobilizing a high density of nucleic acids on an insoluble surface, which are particularly useful for mass spectrometric detection of nucleic acids, are disclosed. Arrays containing the immobilized nucleic acids and use of the immobilized nucleic acids in a variety of solid phase nucleic acid chemistry applications, including nucleic acid synthesis (chemical and enzymatic), hybridization and/or extension, and sequencing, are provided. Serial and parallel dispensing tools that can deliver defined volumes of fluid to generate multi-element arrays of sample material on a substrate surface are further provided. Tools provided herein can include an assembly of vesicle elements, or pins, wherein each of the pins can include a narrow interior chamber suitable for holding nanoliter volumes of fluid. Methods for dispensing tools that can be employed to generate multi-element arrays of sample material on a substrate surface are also provided. 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 may be passed to a plate assembly that disposes the sample arrays for analysis by mass spectrometry.

High density immobilization of nucleic acids

Fully automated modular analytical systems with integrated instrumentation for analysis of biopolymer samples, such as nucleic acids, proteins, peptides and carbohydrates, are provided. Analytical methods of detection and analysis, such as mass spectrometry, radiolabeling, mass tags, chemical tags and fluorescence chemiluminescence, are integrated with robotic technology and automated chemical reaction systems to provide a high-throughput, accurate Automated Process Line (APL).

Automated process line

Fast and highly accurate mass spectrometry-based processes for detecting particular nucleic acid molecules and sequences in the molecules are provided. Depending upon the sequence to be detected, the processes, for example, can be used to diagnose a genetic disease or a chromosomal abnormality, a predisposition to a disease or condition, or infection by a pathogen, or for determining identity or heredity. One aspect provides a process for determining whether a target nucleotide is present in a nucleic acid molecule including hybridizing a nucleic acid molecule with a primer oligonucleotide; contacting the hybridized primer with deoxyribonucleoside triphosphates, chain terminating nucleotides and a DNA polymerase, whereby the hybridized primer is extended until a chain terminating nucleotide is incorporated, producing an extended primer, and determining the molecular mass of the extended primer, thereby determining whether the target nucleotide is present in a nucleic acid molecule.

DNA diagnostics based on mass spectrometry

Fast and highly accurate mass spectrometry-based processes for detecting particular nucleic acid molecules and sequences in the molecules are provided. Arrays of oligonucleotides for performing mass spectrometric analyses are provided. In one aspect, a solid support is provided that includes a plurality of single-stranded oligonucleotides immobilized thereon by a linker cleavable under conditions of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry; and matrix for performing MALDI mass spectrometry, wherein the support comprises a flat surface.

Solid support for mass spectrometry

Serial and parallel dispensing tools that can deliver defined and controlled volumes of fluid to generate multi-element arrays of sample material on a substrate surface are provided. The substrates surfaces can be flat or geometrically altered to include wells of receiving material. Also provided are tools that allow the parallel development of a sample array. To this end, the tool can be understood as an assembly of vesicle elements, or pins, where each of the pins can include a narrow interior chamber suitable for holding nanoliter volumes of fluid. Each of the pins can fit inside a housing that forms an interior chamber. The interior chamber can be connected to a pressure source that will control the pressure within the interior chamber to regulate the flow of fluid within the interior chamber of the pins. The prepared sample arrays can then be passed to a plate assembly that disposes the sample arrays for analysis by mass spectrometry.

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

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

Open systems for performing submicroliter reactions are provided. The systems can include a support for performing the reaction; a liquid dispensing system for dispensing a submicroliter amount of a liquid to a site on or in the support; a temperature controlling device for regulating the temperature of the support; and an interface for controlling the amount of liquid dispensed from the liquid dispensing system are provided. Methods using the systems are also provided.

Systems and methods for performing reactions in an unsealed environment

This invention relates to methods for detecting and sequencing of target double-stranded nucleic acid sequences, to 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 probe 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 nucleic acids 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 determination of molecular weights and identification of the target sequence.

Solid phase sequencing of double-stranded nucleic acids

The invention provides fast and highly accurate mass spectrometer based processes for detecting a particular nucleic acid sequence in a biological sample. 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.

A process for determining the identity of a target polypeptide using mass spectroscopy is provided. Depending on the target polypeptide to be identified, a process as disclosed can be used, for example, to diagnose a genetic disease or chromosomal abnormality, a predisposition to a disease or condition, or infection by a pathogenic organism; or for determining identity or heredity. Kits for performing the disclosed processes also are provided.

Mass spectrometric detection of polypeptides

A method for dissociating a complex of a biotin compound and a biotin-binding compound, by contacting the complex with an amine, is disclosed.

Growing community of inventors

La Jolla, CA, United States of America

Hubert Köster

Growing community of inventors

La Jolla, CA, United States of America

Hubert K&ouml;ster

Hubert Köster