Abstract: The present invention provides modified oligonucleotide primers designed to incorporate a cleavable moiety so that a 3? portion of the primer (linked to an extension product) can be released from an upstream 5? portion of the primer. Upon selective cleavage of the cleavable site, primer extension products that contain about five or fewer base pairs of the primer sequence are released, to provide more useful sizing and sequence information per fragment than extension products containing the entire primer.

Abstract: The present invention relates to a method for genotyping a diploid organism to detect single nucleotide polymorphisms (SNPs) using modified nucleotides or nucleotide residues substituted with fluorescent groups.

Abstract: 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.

Abstract: Matrix assisted laser desorption/ionization (MALDI) is performed in a manner that thermalizes large analyte ions in a plume of desorbed material for spectroscopic analysis. The thermalized ions have a low or zero mean velocity and are presented at a well-defined instant in time, reducing artifacts and sharpening the spectral peaks. In one embodiment the light is delivered to a matrix or sample holder having a cover, baffle or compartment. The baffle or compartment impedes or contains a plume of desorbed material and the analyte undergoes collisions to lower its mean velocity and directionality. Thus “thermalized” the analyte ions are passed to a mass analysis instrument.

Abstract: The present invention is related to the fields of genetic mapping and genetic identity detection, including forensic identification and paternity testing. This invention is more specifically directed to the use of mass spectrometry to detect length variation in DNA nucleotide sequence repeats (including variants of common alleles), such as microsatellites and short tandem repeats, and to DNA sequences provided as primers for the analysis of DNA tandem nucleotide repeat polymorphisms at specific loci on specific chromosomes.

Abstract: 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).

Abstract: Mass spectrometry of large nucleic acids by infrared Matrix-Assisted Laser Desorption/Ionization (MALDI) using a liquid matrix is reported.

Abstract: Mass spectrometry of large nucleic acids by infrared Matrix-Assisted Laser Desorption/Ionization (MALDI) using a liquid matrix is reported.

Abstract: Using nonvolatile, releasable, mass-labels, the present invention provides for the synthesis and use of mass-labeled compounds to specifically interact with biomolecular targets. Following binding of the mass-labeled compounds to the target molecule, the unique mass-label can be analyzed using mass spectrometry to identify and characterize the target molecule. In one embodiment of the invention, a mass-labeled oligonucleotide probe is used to identify a specific gene sequence. A myriad of mass-labeled compounds may be produced for use in a wide variety of interactions such as oligonucleotide-oligonucleotide hybridization, polynucleotide-polynucleotide interactions, enzyme-substrate or substrate analog/intermediate interactions, polypeptide-nucleic acid interactions, protein-ligand interactions, receptor-ligand interactions, polypeptide-metal interactions, nucleic acid-metal interactions or antigen-antibody interactions.

Abstract: 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.

Abstract: 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.

Abstract: A sample preparation system provides an automated process that dispenses appropriate amounts of solid material into wells of a microtiter plate for mixing into a suspension. The system utilizes an array of hollow tubes that are lowered into a particle reservoir such that particle material is forced up into the tubes. During loading, solid plungers in the tubes are positioned a known distance from the open end of the tubes. When the particle material is to be dispensed, the plungers are lowered to push the particle material out of the tubes and into receiving wells of the microtiter plate. The plunger stroke and internal diameter of the tubes defines the dispensed volume of particle material.

Abstract: Disclosed is a process line system for handling biological samples. The system includes a control computer that controls the movement of a sample material plate along the process line. The control computer accepts user inputs that define handling of the biological samples. The system further includes a plurality of modules arranged along the process line. Each module includes at least one work station that performs at least one task associated with the handling of the biological samples. The control computer adjusts the movement of the sample material plate along the process line so that the sample material plate is transported to only those modules that are to handle the biological sample, and so that the sample material plate bypasses any module that should not handle the biological sample, as defined by the user inputs.

Abstract: 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.

Abstract: This invention relates to methods for screening nucleic acids for polymorphisms by analyzing amplified target nucleic acids using mass spectrometric techniques and to procedures for improving mass resolution and mass accuracy of these methods of detecting polymorphisms.

Abstract: Mixtures containing a biological macromolecule, such as a nucleic acid molecule or a polypeptide, and a liquid matrix, which absorbs infrared (IR) radiation, are provided. These mixtures are useful for analysis of the biological macromolecule by IR matrix assisted laser desorption/ionization (IR-MALDI) mass spectrometry. Also provided are processes for analyzing a biological macromolecule using IR-MALDI mass spectrometry. For example, processes for detecting the presence or identity of a biological macromolecule in a sample, or for sequencing a biological macromolecule are provided.

Abstract: Systems and methods for testing samples, particularly biological samples are provided. The system includes an instrument for detecting molecules in samples, and a processor that communicates with the instrument to provide results-based control of the instrument to effect assay-based judging. For example, a system, including software, is provided that directs and performs assays such as diagnostic assays that employ a mass spectrometer. The output of the system, rather than a mass spectrum or other raw data form, is the diagnostic outcome, such as a genotype.

Abstract: 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.

Abstract: 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.

Abstract: The method for testing a biological sample operates on a testing system. The testing system generally comprises an instrument that is configured to acquire data from a biological sample and a processor. In performing the method for testing, the instrument acquires data from the biological sample, and the processor compares the acquired data to predefined data criteria. Responsive to comparing the acquired data to the data criteria, the instrument may be adjusted, and another data set acquired. In one disclosed example of the testing system, a mass spectrometer acquires data from a biological sample. The acquired data is compared to predefined spectrum criteria. Responsive to the comparison, the mass spectrometer may be directed to resample the biological sample or proceed to another sample.