Abstract: Disclosed is a modular fluorescence sensor having the following general formula: where Fl is a fluorophore, N is a nitrogen atom, Bd1 and Bd2 are independently selected binding groups, Sp is an aliphatic spacer, and An is an anchor group for attaching the sensor to solid substrates. n=1 or 2, m=1 or 2, x is an integer, and y=1 or 2. The binding groups are capable of binding an analyte molecule to form a stable 1:1 complex. In a preferred embodiment, the Bd1 is R1—B(OH)2 and Bd2 is R2—B(OH)2. R1 and R2 are aliphatic or aromatic functional groups selected independently from each other and B is a boron atom. The present invention also provides methods of synthesizing a modular fluorescence sensor and its use in labeling solid substrates.

Abstract: A removable adapter for a centrifuge container is described. The adapter has an opening on top, an exterior surface and an interior surface. The exterior surface of the adapter body completely conforms to the bottom portion of the centrifuge container cavity. The interior surface of the adapter body has an internal sidewall and a bottom with a pellet well. The pellet well extends downwardly, toward the exterior surface. Also, an assembly is disclosed, including the adapter of the present invention with a pellet well and a liner, conforming to the interior surface of the adapter, once inside the adapter. Also provided by the present invention is a method for separating solids from suspensions by centrifugation. In this method, the removable adapter with a pellet well of the present invention is placed into a centrifuge container. Then, the suspension is placed into the centrifuge container. When centrifugation is completed, the pellet is removed from the pellet well.

Abstract: An article of manufacture is provided that is useful in differentiating between solutes, such as during electrophoretic separations. An embodiment of the article is a capillary tube, that carries a polymer along the inner wall of the capillary tube. The polymer is effective to reduce undesired interactions and preferably includes a polylactam that is absorbed to the surface before the surface is exposed to the solutes. A preferred polylactam is poly(vinylpyrrolidone) with a molecular weight greater than about 1,000,000 daltons (weight-average).

Abstract: Minimally invasive methods for measuring an analyte, such as glucose, contained in tile interstitial fluid of a body are provided. The methods include the steps of. (a) providing at least one sensor particle capable of generating a detectable analyte signal in responding to the analyte concentration of the body, (b) placing the sensor particle into the skin of the body for allowing the sensor particle to be in contact with the interstitial fluid of the body to generate the detectable analyte signal, (c) detecting the generated analyte signal, and (d) determining the concentration of the analyte contained in the interstitial fluid. The sensor particles may be made to be responsive to an analyte such as glucose concentration contained in a body fluid by including a photo-induced electron transfer receptor specific for the analyte in the sensor particle.

Abstract: This invention provides dyes, particularly cyanine and related dyes, with acyl fluoride activating groups, the dyes having the general formula wherein: each dotted line represents carbon atoms necessary to form a fused substituted or unsubstituted aromatic ring; n is an integer selected from the group consisting of 1, 2 and 3; X and Y are selected from the group consisting of S, O, N, CH2 and C(CH3)2; at least one of said R1 and R2 comprises a sulfonic acid or sulfonate group attached to the aromatic ring; and R3 and R4 are independently selected from the group consisting of alkylcarboxylate, activated alkylcarboxylate and an inert group; wherein at least one of said R3 and R4 groups is alcylcarboxylate or activated alkylcarboxylate with the carboxyl group converted to an acyl fluoride. The inert group is a group that is inert towards acyl fluoride and has a sterical structure which allows aminoacylation of the acyl fluoride group.

Abstract: This invention provides cyclic-bridged dyes, particularly cyclic-bridged cyanine dyes, of the general formula: In this formula, each dotted line represents carbon atoms necessary to form a fused substituted or unsubstituted aromatic ring; n=1-18; m=1-18, selected independently from n. X and Y are selected independently from the group consisting of S, O, N, CH2 and C(CH3)2; at least one of said R1 and R2 comprises a sulfonic acid or sulfonate group attached to the aromatic ring; and R3 and R4 are independently selected from the group consisting of carboxyl, activated carboxyl and methyl, wherein at least one of said R3 and R4 groups is carboxylate or activated carboxylate. Methods of making and using the cyclic-bridged dyes are also provided.

Abstract: This invention provides dye phosphoramidites, particularly phosphoramidites of cyanine and related dyes, of the general formula: In this formula, each dotted line represents carbon atoms necessary to form a fused substituted or unsubstituted aromatic ring; m is an integer from 1 to 18; Y and Z are independently selected from the group consisting of S, O, N, CH2 and C(CH3)2; R1 is an alkyl; (PAM) is a phosphoramidite group; X⊖ is a negative ion; and Q is or wherein n is 1, 2 or 3. Methods of making and using the dye phosphoramidites are also provided.

Abstract: The separation of enantiomeric pairs of compounds by capillary electrophoresis using highly sulfated &agr;-, &bgr;-, and &ggr;-cyclodextrins as chiral selectors is described herein. These charged cyclodextrins have a higher degree of sulfation and narrower heterogeneity than previous cyclodextrin derivatives. CE analyses using highly sulfated cyclodextrins produce improved resolution of a wide variety of chiral drugs, particulaly neutral compounds and amines. The highly sulfated &agr;-,&bgr;-, and &ggr;-cyclodextrins produce separations which complement each other to further expand the number of neutral and basic drugs that can be resolved by capillary electrophorsis.

Abstract: Reagents and methods for preparing samples containing both biomolecule analytes and macrobiomolecules for capillary electrophoresis separation are provided. The reagents comprise a branched polymer. When mixed with a sample containing both biomolecule analytes and macrobiomolecules, particularly DNA templates, the branched polymer of the reagent can suppress the entrance of the macrobiomolecules into a capillary electrophoresis tube during electrokinetic injection of the sample into the capillary electrophoresis tube.

Abstract: A modified Edman degradation process is used to obtain compositional tags for proteins. The Edman degradation chemistry is separated from amino acid analysis, circumventing the serial requirement of the conventional Edman process. Multiple cycles of coupling and cleavage are performed prior to extraction and compositional analysis of amino acids. The amino acid composition information is used to search a database of known protein or DNA sequences to identify the sample protein.

Abstract: A method of attaching unmodified biopolymers, particularly, unmodified polynucleotides, directly to a solid support is provided. The method includes the steps of (a) providing unmodified biopolymers; (b) providing a solid support having at least one surface comprising pendant acyl fluoride functionalities, and (c) contacting the unmodified biopolymers with the solid support under a condition sufficient for allowing the attachment of the biopolymers to the solid support. The unmodified biopolymers may be nucleic acids, polypeptides, proteins, carbohydrates, lipids and analogues thereof. The unmodified polynucleotides may be DNA, RNA or synthesized oligonucleotides. The DNA may be single or double stranded. A device including a solid support and unmodified biopolymers attached to the solid support by reaction with the pendant acyl fluoride functionalities of the solid support is also provided. The methods and devices of the present invention may be used in performing hybridization assays and immunoassays.

Abstract: Disclosed herein are methods for the detection and exponential amplification of a target nucleic acid sequence. In a preferred embodiment, the methodology relies upon three oligonucleotide moieties: a Blocker moiety capable of hybridizing to a target sequence; a Primer moiety capable of hybridizing to the target sequence in an adjacent fashion to the Blocker moiety; and an End-Run moiety having a sequence which is complementary to the Blocker moiety. A ligation event between the hybridized Blocker and Primer moieties, followed by elongation of the End-Run moiety along the ligated Blocker and Primer moieties, provides multiple copies of target sequence such that during cyclical amplification, exponential amounts of the original target sequence are provided.

Abstract: The disclosed invention is a ceramic composition and a process for forming thin tapes and bodies with minimal and controllable firing-induced shrinkage. The composition comprises a refractory component, a glass component and may also include a metal component. The glass component should have no more than about five percent of particles less than 10 microns. The glass component is not milled with the refractory component. They are briefly blended, e.g., by high shear mixing, in a manner which will preserve the particle size and particle size distribution of the glass. The resultant mixture is cast into a sheet or tape, with minimal or no pressure, dried and fired.

Abstract: Methods for profiling oligosaccharides released from glycoproteins and methods for the electrophoretic separation of high mannose, complex and hybrid oligosaccharides are disclosed. The disclosed methods include first providing an analytical sample which includes at least one released oligosaccharide and introducing the sample into an electrophoretic channel containing an electrophoretic separation medium having a pH less than 8 and greater than 2.5.Then applying a sufficiently high electric field causes the released oligosaccharides to electrophoretically migrate and separate within the electrophoresis channel in accordance with their molecular size or charge to mass ratio. Detecting the separated oligosaccharides provides glycoprotein conjugate profiling information. Preferred embodiments include using an electrophoresis separation medium which includes a lithium acetate buffer having pH of about 4.75 and a gel of about 0.4 wt % polyethylene oxide.

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: 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: This invention provides a hard, strong ceramic body and method of manufacture whereby the body, after being formed into the desired shape and size can then be fired into a monolithic structure without any shrinkage or distortion during the firing operation. The "green," unfired ceramic composition comprises one or more powdered refractories and one or more powdered glasses which have a melting point below the softening point of the selected refractory material. Preferred refractories are alumina and zirconia; preferred glasses are lead borosilicate and barium borosilicate. The composition may also contain a metal powder.

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: The filing of an internally coated capillary with a gel in its polymerized state without damaging the gel. The coating prevents bonding of the gel to the inside of the capillary. The gel comprises up to 6% acrylamide and 0-5% crosslinker. The gel can be advantageously and conveniently used in automated electrophoresis systems for automatic replacement of spent gel.

Abstract: The filling of an internally coated capillary with a gel in its polymerized state without damaging the gel. The coating prevents bonding of the gel to the inside of the capillary, The gel comprises up to 6% acrylamide and 0-5% crosslinker. The gel can be advantageously and conveniently used in automated electrophoresis systems for automatic replacement of spent gel.