Abstract: Deoxyribonucleotide and ribonucleotide derivatives of the general formula I ##STR1## wherein R.sup.1 represents --CR'R"--Ar, in which Ar is substituted aryl (as hereinafter defined) and R' and R" are independently selected from the group consisting of hydrogen and lower alkyl; one of --R.sup.2 and R.sup.3 is a hydroxyl-protecting group and the other is a group suitable for synthesis of polynucleotides or for attachment of the nucleotide to a solid support; R.sup.4 is selected from the group consisting of hydrogen, --OH and protected hydroxyl; and B represents a divalent radical corresponding to a purine or pyrimidine base. When synthesis is carried out using these derivatives, the deprotection procedure is reduced to an essentially instantaneous process. The derivatives have acceptable shelf life and are very stable to conventional DNA synthesis conditions. Particularly preferred are those compounds wherein Ar is mono- and dihalo-substituted phenyl.

Abstract: Disclosed herein are protecting groups for exocyclic amino groups of the base cytosine for use in the synthesis of oligonucleotides and oligonucleoside phosphorothioates, the protecting groups being represented by the formula: --CO--(CH.sub.2).sub.0-9 --CH.sub.3. In a particularly preferred embodiment, the base cytosine is protected with acetyl (--CO--CH.sub.3), and the oligonucleotide or oligonucleoside phosphorothioate incorporating the protected cytosine is subjected to a cleavage/deprotection reagent comprising methylamine and ammonia.

Abstract: An analytical system uses a waveguide having embedded Bragg gratings to redirect light from the waveguide outwardly for analytical determination by detectors. The analytical system can be a spectrophotometer, spectrofluorimeter, or other means for analyzing the components of light passed through a sample or emanating from a sample. The system can be single or multi-channeled and can be integrated with a detector onto a single chip device. A manifold with multiple input waveguides and multiple output waveguides is also provided. The interaction point between the input and output waveguides is a target area in which a sample capillary tube can be located.

Abstract: A system and method are disclosed for optically aligning a capillary tube and an excitation laser beam for fluorescence detection applications by utilizing the Raman scatter signals of the capillary tube's contents. For example, Raman scatter by an electrophoretic separation matrix may be used for alignment in a capillary electrophoresis system. Fluorescent material may be present and may also be used for alignment purposes, but is not necessary. The invention employs a parabolic reflector, having apertures through which the capillary tube and the laser beam are guided so that they intersect, preferably at right angles and at the focal point of the reflector. The Raman scatter signals of the material within the capillary tube are collected via a series of filters and this information is used to reposition, if necessary, a focusing lens that directs the excitation beam into the reflector and the capillary tube, so that the Raman scatter signals are maximized.

Abstract: Coated capillary electrophoresis columns and methods for their use in electrophoretic separations are disclosed. The coated capillary columns include a length of tubing having an interior surface having an interconnected polymeric coating. The interconnected polymeric coating includes a hydrophobic hydrocarbon polymeric functionality covalently bound to the interior surface and polyvinylalcohol interconnected with the hydrophobic polymeric functionality. Exemplary columns are prepared by causing a Si-OH reactive compound, having a hydrophobic polymeric functionality, to react with Si-OH functionalities on the interior surface of capillary columns. Then causing vinyl acetate to polymerize in contact with the hydrophobic polymeric functionality and hydrolyzing the resulting polyvinylacetate forms a coating of interconnecting hydrophilic and hydrophobic polymers.

Abstract: A variable inclination centrifugation or rotor assembly and a method for rapid separations. The samples, such as whole blood, are centrifuged within pivoting tube holders while in a first position wherein the longitudinal axes of the tube holders are substantially parallel to a central axis of rotation. As rotation continues, the tube holders are inclined in a radial direction by controlled adjustment of the tube holders toward a second position wherein the axes of the tube holders and the rotation axis are substantially perpendicular. The first embodiment of the assembly employs a worm gear to incline the samples and allows for inclination and rotation of the samples to be controlled independently. The second and third embodiments employ a spring-loaded linkage system and a governor mass and three-arm linkage system, respectively, for inclination. These are activated by the rotational speed of the samples.

Abstract: Disclosed herein are surface activated, organic polymers useful for biopolymer synthesis. Most preferably, aminated polypropylene is used for the synthesis of oligonucleotides thereto, and these devices are most preferably utilized for genetic analysis of patient samples.

Abstract: A process for synthesizing oligonucleotides by phosphoramidite chemistry wherein the improvement is the use of substituted aryl carboxylic acids as the activators. These activators produce in situ nucleotide intermediates in which the substituted arylcarbonyl group has displaced the amidite moiety.

Abstract: Homogeneous immunoassays and enzyme-substrate assays which use capillary electrophoresis and fluoescent detection systems are described. The method is useful for detecting and/or quantitating the concentration of analytes in a sample.

Abstract: Processes for the electrophoretic analysis of monosaccharides and/or polysaccharides are disclosed. The processes generally first include providing a composition having derivatized mono and/or polysaccharide components which are monosaccharide and/or polysaccharide labelled with a fluorescing charged compound. Then introducing the composition into an electrophoretic medium and applying an electric field across the electrophoretic medium causes the derivatized monosaccharide and/or polysaccharide components to differentially migrate within the electrophoretic medium. Then detecting the derivatized monosaccharide and/or polysaccharide components is accomplished by laser exciting the derivatized monosaccharide and/or polysaccharide components and monitoring fluorescent emission of the derivatized monosaccharide and/or polysaccharide components. The processes provide extremely low detection limits of the labelled components.

Abstract: Disclosed herein are surface activated, organic polymers useful for biopolymer synthesis. Most preferably, aminated biaxially oriented polypropylene is used for the synthesis of oligonucleotides thereto, and these devices are most preferably utilized for genetic analysis of patient samples.

Abstract: Nucleic acid probes and protein probes are disclosed. The nucleic acid probe comprises a probe polynucleotide, a charged hapten label, and a binding moiety. The protein probe comprises a probe protein, a charged hapten label and a binding moiety. The charged hapten label joint to the binding moiety can comprise a negatively charged sulfophenylhydrazine tag compound. Polyclonal antibodies and monoclonal antibodies with specific affinity for the charged hapten labels are disclosed as are hybridomas capable of making the monoclonal antibodies. Methods and kits are disclosed for making the nucleic acid probes, making the protein probes, detecting a capture polynucleotide of the nucleic acid probe and detecting a capture molecule of the protein probe.

Abstract: A heated cover for a receptacle containing a vaporizable substance. The cover is heated to a temperature above the temperature of the substance so as to prevent condensation of vapor evaporated from the substance. A device for placing and removing the cover with respect to the receptacle is designed in connection with a temperature-controlled heating/cooling plate which controls the temperature of the contents of the receptacle.

Abstract: An apparatus and method are set for determining the centers of capillaries in a multicapillary electrophoresis array for subsequent rapid and efficient laser induced fluorescence interrogation. A galvometric scanner reflects the laser beam to scan the array during an alignment pre-scan. The beam interacts with the array to produce an intensity pattern indicative of the capillary centers. The scanner positions corresponding to the capillary centers determined during the pre-scan is recalled to direct the beam during the interrogation scan to the column centers.

Abstract: A method for detecting an analyte, in an aqueous solution at a physiological pH, by reductive or oxidative/reductive electrochemical luminescence methodologies is disclosed. The method proceeds by labelling the analyte with a transition metal complex, followed by inducing the transition metal label to luminescence by application of a suitable electrical potential to a solution containing the label and the analyte. The transition metal complex can be a tris-ruthenium(bipyridine) complex. A hydroxylamine and/or a halogen-containing moiety can be used to enhance both reductive and/or oxidative electrochemical luminescence of the transition metal complex. The transition metal chelate can be used as a label for the detection of picomolar concentrations of an analyte of interest, such as an analyte present in a sample of a physiological fluid.

Abstract: An apparatus and method of aligning a capillary with respect to a radiation source. More particularly, the capillary is aligned with a laser beam for laser induced fluorescence detection. The scatter or transmitted light pattern of the laser beam with respect to the capillary tube is utilized to determine optimum alignment. photosensors may be implemented to detect the light pattern which represents optimum alignment. For dynamic alignment during electrophoresis, the photosensors provide feedback to a controller which controls a positioning mechanism for alignment of the capillary.

Abstract: Disclosed are reagents of methods for cleaving and deprotecting insolubilized and protected synthetic oligonucleotides. In a particularly preferred embodiment, the reagent comprises methylamine and t-butylamine.

Abstract: Compositions useful as a separation medium in capillary electrophoresis procedure and methods for their use in capillary electrophoresis are described. The compositions include dry linear polyacrylamide which is capable of hydrating to form an aqueous polymeric system capable of filling an electrophoresis capillary column. Also disclosed are methods for using dry polyacrylamide in capillary electrophoresis. The methods include providing a dry polyacrylamide composition, reconstituting the dry polymer to provide a solution of reconstituted polymer, and causing the reconstituted polymer to fill a capillary electrophoresis column.

Abstract: Processes are provided for pretreating body fluid compositions and subsequently analyzing the pretreated body fluid compositions for analytes of interest. Processes for pretreating the compositions include providing size exclusion gel having a molecular weight fractionation range or a molecular weight exclusion such that the size exclusion gel is capable of excluding or fractionating the analytes of interest, and then causing the composition to contact the size exclusion gel in order to separate the analytes from low molecular weight composition components which interfere with the separation and analysis of the analytes of interest. Processes for analyzing pretreated compositions include electrophoretic methods such as capillary zone electrophoresis which involve the separation and detection of analytes of interest.

Abstract: A sample having both positively and negatively charged components may be separated during the same run by injecting a plug of sample at both ends of the capillary and applying an electric field in the capillary, where there is insufficient electroosmotic flow in the capillary to reverse sample migration direction, such as in the case of a gel-filled column.