Abstract: Binary probe and clamp compositions conduct methods for target hybridization detection. Where the probe is a substrate for exonuclease cleavage, the composition provides quantitation and detection of PCR products, by real-time and end-point measurements. Where the probe is an amplification primer, the composition provides an improved method for labelling and detection of PCR products. Probes and clamps may be labelled with fluorescent dyes, quenchers, hybridization-stabilizing moieties, chemiluminescent dyes, and affinity ligands. Clamps may be nucleic acid analogs, such as 2-aminoethylglycine PNA.

Abstract: The invention provides novel dye-labeled ribonucleotide analogs and methods for synthesizing those analogs. The compounds of the invention are especially useful for DNA sequencing by the polymerase chain reaction.

Abstract: The invention provides novel dye-labeled ribonucleotide analogs and methods for synthesizing those analogs. The compounds of the invention are especially useful for DNA sequencing by the polymerase chain reaction.

Abstract: Disclosed is a method for determining the number of repeat units in a repeat region of a target nucleic acid. In a first aspect, the method of the invention includes the steps of annealing a primer to a target nucleic acid; performing a first primer extension reaction using a first primer extension reagent; separating the target-primer hybrid and unreacted first primer extension reagent; performing a second primer extension reaction using a second primer extension reagent, wherein at least one of the first or second primer extension reagents includes an extendible nucleotide having a label attached thereto; separating the target-primer hybrid from unreacted second primer extension reagent; measuring a signal produced by the label; treating the label so as to render the label undetectable; and repeating the above steps until the signal is substantially less than a signal detected in a previous cycle.

Abstract: A method and apparatus to illuminate a target. The apparatus can comprise a first lens configured to receive light from the light source, a diffractive optical element configured to receive the light from the first lens and to regulate the light into regulated light, and second lens configured to receive the regulated light and to direct the regulated light to a selected area of the target.

Abstract: An optical system for analyzing light from a plurality of samples is provided. The optical system includes a plurality of holders adapted to have samples located therein, a collection lens, a transmission grating, and a reimaging lens. The collection lens is configured to receive and substantially collimate light from the samples. The transmission grating is configured to spectrally disperse the substantially collimated light from the collection lens. The reimaging lens is configured to receive the light from the light dispersing element and direct the light onto a light detection device. A method of optically analyzing at least one sample is also provided.

Abstract: Chemiluminescent heteroaryl substituted benzothiazole 1,2-dioxetane compounds capable of producing light energy when decomposed are provided. These chemiluminescent compounds are represented by the general formula: The heteroaryl substituent Y can be, for example, a pyridyl group or a benzothiazolyl group. The heteroaryl substituted benzothiazole compounds are substantially stable at room temperature. Kits including the heteroaryl substituted dioxetane compounds as well as methods for using these compounds for detecting the presence of one or more analytes in a sample are also provided.

Abstract: The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20° C. to about 50° C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5×103 to about 1×106 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9.

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 3′→5′ 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: The present invention provides substrates and apparatuses for efficient, rapid and specific capture, and optimal recovery, of nucleic acids, as well as methods of their use. The substrate is porous in nature and has a capture polynucleotide capable of hybridizing to a target nucleic acid immobilized thereon. Upon flowing a sample containing or suspected of containing the target nucleic acid through the porous substrate, the target nucleic acid is rapidly captured. Following capture, the target nucleic acid can be efficiently recovered for subsequent use.

Abstract: The present invention provides a process for the removal of protecting groups, i.e. deprotection, from chemically synthesized oligonucleotides. In one embodiment, the invention provides reagents suitable for use in such a process, and kits incorporating such reagents in a convenient, ready-to-use format. By use of the process and reagents of the invention, side-reactions leading to certain impurities that contaminate the synthesized oligonucleotides can be minimized.

Abstract: Propargylethoxyamino nucleosides are disclosed having the structure 1

Abstract: A thermal cycling device for performing nucleic acid amplification on a plurality of biological samples positioned in a sample well tray. The thermal cycling device includes a sample block assembly, an optical detection system, and a sample well tray holder configured to hold the sample well tray. The sample block assembly is adapted for movement between a first position permitting the translation of the sample well tray into alignment with sample block assembly, and a second position, upward relative to the first position, where the sample block assembly contacts the sample well tray. A method of performing nucleic acid amplification on a plurality of biological samples positioned in a sample well tray in a thermal cycling device is also provided.

Abstract: The present invention provides, among other things, supports upon which one or more species can be adsorbed, captured, or immobilized for biochemical procedures. In various embodiments, the supports include a plurality of deformable petal-like members that provide binding sites for biochemical species. The invention provides an apparatus and method for the ready insertion of the petal-like members into respective wells of a multi-well microplate (e.g., a standard-format 96- or 384-well plate).

Abstract: A device for handling PCR microcards, each having an array of sample chambers closed by a transparent material on one side thereof, in relation to a PCR instrument, the device including a carrier having an apertured region with an array of holes corresponding in number and relative location with the array of sample chambers in each of the microcards, and a provision for retaining a microcard on the carrier so that the transparent material faces the apertured region with the reagent sample chambers aligned, respectively, with the holes in the apertured region, and so that the side of the microcard opposite the transparent material is unobstructed at least throughout the array of sample chambers. The device cooperates with the PCR instrument to ensure accurate positioning of the carrier and the microcard retained thereon for real time PCR processing.

Abstract: The invention provides methods and a kit for primer extension of PNA-DNA chimera from template nucleic acids using polymerases, nucleotide 5′-triphosphates, and primer extension reagents. Structural requirements of the chimera for primer extension include 5 to 15 contiguous PNA monomer units, 3 or more contiguous nucleotides, and a 3′ hydroxyl terminus. The chimera and/or a nucleotide is labelled with fluorescent dyes or other labels. The methods include DINA sequencing, DNA fragment analysis, reverse transcription, mini-sequencing, chromosome labelling, amplification, and single nucleotide polymorphism (SNP) detection.

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.

Abstract: The present invention is directed to a system for filling sample chambers with liquid. The system includes a substrate defining the sample chambers and having a fill port, and a network of passageways connecting the sample chambers to the fill port. The system also includes a substrate support to retain the substrate in a fill position and a valve module on the substrate support. The valve module has a fill port seal opening to connect with the fill port of the substrate in the fill position, and a vacuum opening for connection to a source of vacuum. The system further includes a valve body having a liquid outlet port and a vacuum port, and means for operating the valve body so that the liquid outlet port and the vacuum port are alternately in fluid communication with the fill port seal opening.

Abstract: A sample handling system in a multi-channel capillary electrophoresis apparatus is disclosed. The sample handling system includes a work surface for supporting a plurality of samples located at a plurality of work surface coordinates and a sample loading assembly comprising a plurality of loading wells. At least one of the loading wells includes a capillary fixedly positioned therein. The system further includes a programmable sample transfer device for automatically transferring a sample from a work surface coordinate to a loading well. The invention further includes methods for using the sample handling system.

Abstract: The invention provides a collection of probes useful for hybridizing to a target nucleic acid. The probes associate with each other, binding with high affinity to the target nucleic acid, to form three-way junctions and other complexes. At least one of the probes in each collection includes a nucleic acid analog. Methods using the probes in hybridization and as primers are also provided.