Sequenom, Inc.

Agena Biosciences, Inc.

Daniel P Little

Hubert K&ouml;ster

Charles Cantor

Hubert Köster

Andreas Braun

Maryanne J O'Donnell-Maloney

David M Lough

G Scott Higgins

Hubert Koster

Christian Jurinke

Young Tae Kim

Dirk Johannes Van Den Boom

Franz Hillenkamp

Dirk Van Den Boom

Andreas Ruppert

Dong-Jing Fu

Brigitte Darnhofer-Demar

Guobing Xiang

Maryanne J Little

Young-Soo Kwon

Changwon Kang

Scott Higgins

G Scott Higgens

Kai Tang

Carsten W Siegert

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

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.

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. 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.

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.

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 mass spectrometric method for sequencing nucleic acids using RNA polymerases, including DNA-dependent and RNA-dependent RNA polymerases, is provided. The methods use a modified Sanger sequencing strategy in which RNA polymerase is used to generate a set of nested RNA transcripts obtained by base-specific chain termination. These are analyzed by mass spectrometry. A method of identifying transcriptional terminator sequences or attenuator sequences is also provided.

Mass spectrometric methods for sequencing nucleic acids

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.

The invention provides a means of detecting and identifying mutations in a genetic region, and a means of quantifying the number of repeat units in, for example, a trinucleotide repeat, by transcription/translation of the genetic region into a target polypeptide. The method requires neither radioisotopic nor fluorescent labeling of the target polypeptide. In particular, the invention is based on mass spectrometric determination of the mass of the encoded target polypeptide and comparison of the mass of the polypeptide with its own expected mass or with the mass of a polypeptide of known identity. Depending on the target polypeptide to be identified, 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.

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Patton, PA, United States of America

Daniel P Little