Abstract: In various embodiments, provided are ion optics systems comprising two or more pairs of ion condensers arranged where the first member and second member of each pair are disposed on opposite sides of a first plane such that the first member of the pair has a position that is substantially mirror-symmetric about the first plane relative to the position of the second member of the pair and wherein the deflection angle of each of the ion condensers is less than or equal to about ? radians.

Abstract: Method and system providing calibration of light detected from biological samples with a correction factor including components for each of a plurality of spectrally distinguishable species and/or for each well and/or for each filter.

Abstract: Fluorescent polymeric materials are disclosed comprising a polymer and one or more lipid soluble rhodamine dyes. The materials are especially useful in the preparation of multicolored microparticles, especially multicolored polystyrene microparticle, for use in the multiplexed analysis of a plurality of analytes in a single sample. When excited by a light source, the materials give off a unique emission based on the nature, concentration and ratio of the dyes therein. Methods of preparing and using said materials are also disclosed.

Abstract: A device is provided that can include at least one gas trap that can be arranged in fluid communication with a sample-containment feature formed in or on the device. The gas trap can be arranged to trap gas or air displaced from the sample-containment feature as the sample-containment feature is loaded with a liquid. The trapped gas in the gas trap can assist in breaking-up and expelling the liquid from the sample-containment feature during a subsequent liquid transfer operation, for example, to an adjacent sample-containment feature. Systems for processing such a device and methods using such a device are also provided.

Abstract: A method of conducting amplification comprising loading a liquid polynucleotide sample into a well of a microplate and covering the well of the microplate with a cover, such that the cover fluidly seals the liquid polynucleotide sample within the well. The method then comprises inverting the microplate such that the liquid polynucleotide sample contacts the cover; and thermocycling the microplate to promote amplification of polynucleotides in the liquid polynucleotide sample.

Abstract: System and method for fluorescent light excitation and detection from samples to enhance the numerical aperture and/or reduce the cross-talk of the fluorescent light.

Abstract: An apparatus for detecting analytes in a sample is provided. The apparatus can include: a flow cytometry system including one or more detection zones; one or more irradiation sources disposed for irradiating the one or more detection zones with radiation; at least one detector disposed for collecting charges corresponding to light signals emitted from detectable analytes in the one or more detection zones, which have been excited by the radiation, wherein at least one detector includes an output; a system coupled to the at least one detector for effecting time delay integration of the charges by accumulating the charges before reading the charges at the output of the at least one detector; and a sorting mechanism, for example, to effect flow cytometry. Methods for detecting analytes in a sample are also provided.

Abstract: The invention provides novel nucleic acid polymerases from strains GK24 and RQ-1 of Thermus thermophilus, and nucleic acids encoding those polymerases, as well as methods for using the polymerases and nucleic acids.

Abstract: Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers facilitate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R21Z1C(O)R22R28 where R21 is a C1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z1 is either NH, sulfur or oxygen, R22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R28 includes a functional group which attaches the linker to the acceptor dye.

Abstract: An apparatus for normalizing a PCR instrument, can comprise a microplate comprising at least 6,000 wells and a system of dyes at known concentrations in a plurality of the at least 6,000 wells. A method for normalizing a system can comprise (a) providing a microplate comprising at least 6,000 wells and a system of dyes; (b) exciting at least one dye; (c) detecting an emission output for the at least one dye; (d) determining if the emission output is in an acceptable range; and (e) adjusting the system so that the emission output is in the acceptable range.

Abstract: Disclosed, among other things, are primers containing certain modified nucleobases in the 3? terminal region of the primers that provide reduced formation of primer-dimers during amplification reactions, and various methods of use thereof.

Abstract: Disclosed is a kit useful for determining the number of repeat units in a repeat region of a target nucleic acid comprising: a plurality of different-sequence primers, each containing (i) a target binding segment and (ii) a tag segment having a nucleotide sequence that uniquely identifies the target binding segment, a first primer extension reagent; and a second primer extension reagent, wherein at least one of the first or second primer extension reagents includes an extendible nucleotide having a photodestructible label attached thereto.

Abstract: An oligonucleotide probe is disclosed, the probe including an oligonucleotide, a fluorescer molecule attached to a first end of the oligonucleotide and a quencher molecule attached to the opposite end of the oligonucleotide. The probe is rendered impervious to digestion by the 5??3? exonuclease activity of a polymerase and the 5??3? extension of by a polymerase. The invention also includes methods for performing combined PCR amplification and hybridization probing, one such method including the steps of contacting a target nucleic acid sequence with PCR reagents and an oligonucleotide probe as described above, and subjecting these reagents to thermal cycling. One preferred refinement of the above method further includes the addition of a strand displacer to facilitate amplification.

Abstract: In various aspects, the present teachings provide labeling reagents and sets of labeling reagents for the relative quantitation, absolute quantitation, or both, of hydroxylated compounds including, but not limited to, hydroxylated ring containing compounds, steroids and sterols. In various aspects, the present teachings also provide methods for the analysis hydroxylated compounds including, but not limited to, hydroxylated ring containing compounds, steroids and sterols my MS/MS methods.

Abstract: Nucleic acid sequences are detected by a multi-step process, involving labeling sample nucleic acid sequences, duplexing the labeled sample with a probe having a coupling element, immobilizing all of the duplexed probe and target sequence and unduplexed probe, separating specifically immobilized nucleic acid from free and non-specifically immobilized nucleic acid, releasing specifically immobilized nucleic acid, and detecting the presence of the sequence of interest by means of the label. The labeled sequence may be characterized by sizing, e.g. electrophoresis. The method provides for a sensitive and rapid means for accurate detection of sequences of interest in a wide variety of situations.

Abstract: An automated apparatus is programmed to perform a process by arranging a sequence of first icons on a display in the order of the process, wherein the first icons represent functions of the apparatus, and wherein at least one of the first icons provides a visual representation of a function of the apparatus. Said at least one of the first icons can be expanded to show second icons that comprise the function of said at least one of the first icons, and at least one of the second icons provides a visual representation of a subfunction of the apparatus. In a preferred mode, when said at least one of the first icons is expanded, said at least one of the first icons maintains its same sequential relationship on the display to the other of the first icons in the sequence as before it was expanded.

Abstract: A manifold block and valving system using the manifold block are provided, which are used for conducting chemical reagents, solvents, and other fluids. The manifold block includes a "straight-through" common passage in fluid connection with several entry ports, including also a number of projections in the common passage in the vicinity of the entry ports. These projections partially obstruct the fluid flow, causing a turbulence that provides a washing action in those port regions. The manifold may be constructed of a photosensitive glass ceramic such as Fotoceram.TM. which consists of a number of layers which have been processed to form the manifold block, or of other suitable materials such as silicon.

Abstract: Method and kits are provided for detecting one or more target nucleic acids. A first oligonucleotide having a 3' amino group and a second oligonucleotide having a 5' phosphate group are annealed to a contiguous complementary region of a target nucleic acid. Whenever the 3' terminal nucleotides of the first oligonucleotide and the 5' nucleotides of the second oligonucleotide are complementary to the opposing nucleotides on the target nucleic acid, a nucleic acid ligase ligates the first and second oligonucleotides via the formation of a phosphoramidate linkage. The presence of the target nucleic acid is determined by detection of the ligated first and second oligonucleotides.

Abstract: A method of testing for the presence or absence of a target sequence in a mixture of single-stranded nucleic acid fragments is disclosed. The method involves reacting a mixture of single-stranded nucleic acid fragments with a first probe which is complementary to a first region of the target sequence, and with a second probe which is complementary to a second region of the target sequence, where the first and second target regions are contiguous with one another, under hybridization conditions in which the two probes become stably hybridized to their associated target regions. Following hybridization, any of the first and second probes hybridized to contiguous first and second target regions are ligated, and the sample is tested for the presence of expected probe ligation product. The presence of ligated product indicates that the target sequence is present in the sample.

Abstract: Method and composition for detecting one or more selected polynucleotide regions in a target polynucleotide. In one embodiment of the invention, a plurality of different-sequence probe pairs are added to a target polynucleotide, where each probe pair includes two polynucleotide probe elements which are complementary in sequence to adjacent portions of a selected one of the target sequences in the target polynucleotide. In each probe pair, one of the probe elements contains a non-polynucleotide polymer chain which imparts a distinctive mobility to the associated probe pair, when the elements in the pair are ligated. The other element in the pair contains a detectable reporter label. After the probe pairs have been allowed to hybridize with the target polynucleotide, the hybridized polynucleotides are treated under conditions effective to ligate the end subunits of target-bound probe elements when their end subunits are base-paired with adjacent target bases.