The Perkin-elmer Corporation

Applied Biosystems, LLC

Applera Corporation

Other

Pe Corporation (ny)

Stephen E Moring

Mark F Oldham

Jon A Hoshizaki

Kevin S Bodner

Jason H Halsey

Alfred P Madden

Mark T Reed

Dennis E Mead

Claudia Chiesa

David M Demorest

Ward Kevin Frye

Joseph Jackson

Richard T Reel

Reid Burton Kowallis

Michael S Albin

Ralph Somack

Joseph H Jackson

Thomas E Lee

Timothy S Orpin

Janice C Woods

John H Nickel

The present invention provides multi-well plates and column arrays in which samples (e.g., cell lysates containing nucleic acids of interest, such as RNA) can be analyzed and/or processed. In one embodiment, the microfiltration arrangement is a multilayer structure, including (i) a column plate having an array of minicolumns into which samples can be placed, (ii) a discrete filter element disposed in each minicolumn, (iii) a drip-director plate having a corresponding array of drip directors through which filtrate may egress, and (iv) a receiving-well plate having a corresponding array of receiving wells into which filtrate can flow. The invention provides multi-well microfiltration arrangements that are relatively simple to manufacture and that overcome many of the problems associated with the prior arrangements relating to (i) cross-contamination due to wicking across a common filter sheet or (ii) individual filter elements entrapping sample constituents within substantial dead volumes. Further, the invention provides multi-well microfiltration arrangements that adequately support discrete filter elements disposed in the wells without creating substantial preferential flow. Additionally, the invention provides multi-well microfiltration arrangements that avoid cross-contamination due to aerosol formation, pendent drops and/or splattering. Other disclosed features of the invention provide for the automated covering or heat-sealing of filtrate samples separately collected in an array of wells.

Apparatus and method for avoiding cross-contamination due to pendent drops of fluid hanging from discharge conduits

Multi-well microfiltration apparatus and method for avoiding cross-contamination

Multi-well microfiltration apparatus

Disclosed is a method for increasing the electroosmotic flow rate available for a silica surface. In the method, there is provided an electrophoretic channel which is defined by one or more silica surfaces. The surface(s) are contacted with an alkaline aqueous solution containing a solubilized silicate-monovalent metal complex in an amount effective to increase the acidity of the silica surface(s), as evidenced by a reduction in the average bulk pKa of the surface(s). The achieved increase in acidity is greater than would be obtained using an otherwise identical solution lacking said silicate. In one preferred embodiment, the monovalent metal used in the solution is Li,, Na,, or K,. Also disclosed is a method for increasing the acidity of a silica surface, by contacting the surface with an alkaline aqueous solution of the type noted above.

Method and silicate composition for conditioning silica surfaces

The present invention provides multi-well plates and column arrays in which samples (e.g., cell lysates containing nucleic acids of interest, such as RNA) can be analyzed and/or processed. In one embodiment, the microfiltration arrangement is a multilayer structure, including (i) a column plate having an array of minicolumns into which samples can be placed, (ii) a discrete filter element disposed in each minicolumn, (iii) a drip-director plate having a corresponding array of drip directors through which filtrate may egress, and (iv) a receiving-well plate having a corresponding array of receiving wells into which filtrate can flow. The invention provides multi-well microfiltration arrangements that are relatively simple to manufacture and that overcome many of the problems associated with is the prior arrangements relating to (i) cross-contamination due to wicking across a common filter sheet or (ii) individual filter elements entrapping sample constituents within substantial dead volumes. Further, the invention provides multi-well microfiltration arrangements that adequately support discrete filter elements disposed in the wells without creating substantial preferential flow. Additionally, the invention provides multi-well microfiltration arrangements that avoid cross-contamination due to aerosol formation, pendent drops and/or splattering. Other disclosed features of the invention provide for the automated covering or heat-sealing of filtrate samples separately collected in an array of wells.

The invention relates to new methods of RNA isolation that exploit the surprising discovery that RNA may be differentially precipitated from DNA. The subject methods result in the formation of an RNA-containing precipitate that has an RNA content at least two fold enriched with respect to DNA, as compared with the RNA to DNA ratio of the solution from which the RNA-containing precipitate is derived. The invention also includes various methods of DNA isolation that employ the selective precipitation of RNA. The degree of RNA enrichment achieved is often much greater than two fold; enrichment by a factor of ten or greater is frequently obtained. By precipitating RNA from a solution, the RNA may be collected by simple procedures such as centrifugation or filtration, thereby avoiding the need to bind the RNA to solid phase. The collected RNA precipitate may then be solubilized. One embodiment of the subject methods involves forming an RNA-containing nucleic acid composition, adding an RNA precipitate forming chaotropic salt to the nucleic acid composition in a sufficient concentration to form an RNA-containing precipitate, collecting the RNA-containing precipitate, and (optionally) solubilizing the precipitate. Preferred precipitate forming chaotropic salts are guanidine hydrochloride and guanidine thiocyanate. Other embodiments of the invention include kits for performing the methods of the invention. The invention also includes systems for performing the methods of the invention.

Methods of nucleic acid isolation

Disclosed is a method for increasing the electro-osmotic flow rate available for a silica surface. In the method, there is provided an electrophoretic channel which is defined by one or more silica surfaces. The surface(s) are contacted with an alkaline aqueous solution containing a solubilized silicate-monovalent metal complex in an amount effective to increase the acidity of the silica surface(s), as evidenced by a reduction in the average bulk pKa of the surface(s). The achieved increase in acidity is greater than would be obtained using an otherwise identical solution lacking said silicate. In one preferred embodiment, the monovalent metal used in the solution is Li.sup.+, Na.sup.+, or K.sup.+. Also disclosed is a method for increasing the acidity of a silica surface, by contacting the surface with an alkaline aqueous solution of the type noted above.

An instrument for capillary electrophoresis has a vertically translatable carrier holding one end of the capillary and an electrode connected to a power supply, and a rotary carousel for presenting containers of sample and buffer solutions to a load position where the end of the capillary and the electrode may be inserted by operating the carrier. The other end of the capillary and a second electrode connected to the power supply are immersed in an outlet buffer reservoir. The instrument has a vacuum supply for providing a relative vacuum over the solution in the outlet buffer reservoir, so simple material may be injected into the capillary either by electromigration or by differential pressure. After injection, the first end of the capillary and the electrode may be immersed in buffer to accomplish electrophoresis. By manipulating the carousel and carrier, multiple samples may be electrophoresed in series. In a preferred embodiment the instrument includes a flexible duck-billed septum for closing containers while permitting easy access for the electrode and the capillary tube. Also in a preferred embodiment the instrument is controlled by a microprocessor-based controller.

Capillary electrophoresis

A detector cell, having a capillary entrance elbow through which a beam of exposing light can be directed into the bore of a central leg of the detector cell capillary. Ray traces, to determine the effect of the entrance elbow on the beam of exposing light are used to optimize performance of this detector cell. Back ray tracing is implemented to illustrate an optimized embodiment. Forward ray tracing is also illustrated and can be used to determine system performance for a range or choices of a single parameter or for concurrent ranges of choices of a subset of the parameters of the beam of exposing light.

Capillary detector cell having imaging elements positioned to optimize

A cabinet designed for the storage of basic kitchen utensils, cookware and food stuffs which is designed for use by campers and work crews in remote locations. It consists of a trunk-like cabinet with multiple compartments, a convertible top and front panels which open into a portable kitchen. Unique features include a drawer and slideable trays for maximum accessibility of contents, a paper towel rack, fluorescent lamp and convertible utility compartment.

Camper's chuck cabinet

An apparatus for enhancing signal to noise ratio in the detection of electromagnetic radiation traversing a capillary tube includes a ball lens and a holding element for holding the ball lens and the capillary tube, the holding element having an aperture so that the aperature and the lens together define an optic axis. The holding element is configured to hold the capillary tube such that the center of the capillary tube traverses the optic axis. The lens has a focal length and is held at such a position relative to that focal length by the holding element such that electromagnetic radiation incident on the aperature is focussed to pass radially through the capillary tube. Thus, the effective path length is 100% of the inside diameter of the capillary tube.

Lens for capillary electrophoresis and chromatography

A junction reactor that aligns a pair of capillaries substantially collinearly, end-to-end that allows a small gap to be produced between these two ends. An applied voltage difference between the other ends of these two capillaries produces in the gap electric field lines that extend across the gap. Empirical evidence shows that the gap introduces only a small reduction in resolution of an electrophoretic or electrochromatographic separation. The gap enables sample liquid to be coupled between capillaries of different internal diameters and enables on-capillary reactions such as attaching a fluorescent tag to a sample components.

Growing community of inventors

Lawrence, KS, United States of America

Stephen E Moring